Medicine › Epidemiology

Mycobacterium research and diagnosis

Works Count: 107231

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Description

This cluster of papers focuses on the diagnosis, treatment, and epidemiology of nontuberculous mycobacterial diseases, with a particular emphasis on Mycobacterium avium and Mycobacterium abscessus. It covers topics such as the impact of genotypic studies, antibiotic resistance, prevalence in specific patient populations (e.g., Crohn's disease, cystic fibrosis), and environmental sources. The cluster also delves into genomic and comparative genomic studies supporting the division of the genus Mycobacterium.

Keywords

Nontuberculous Mycobacteria; Mycobacterium avium; Mycobacterium abscessus; Epidemiology; Diagnosis; Treatment; Genomic Studies; Crohn's Disease; Cystic Fibrosis; Antibiotic Resistance

THE PATHOGENESIS OF TUBERCULOSIS

1952-11-01

Arnold R. Rich

Ruminant paratuberculosis (Johne's disease): the current status and future prospects.

1984-07-01

Rodrick J. Chiodini , Herbert J. Van Kruiningen , R. S. Merkal

The Envelope Layers of Mycobacteria with Reference to their Pathogenicity

1997-01-01

Mamadou Daffé , Philip Draper

Epidemiology of Human Pulmonary Infection with Nontuberculous Mycobacteria

2014-11-06

D. Rebecca Prevots , Theodore K. Marras

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Rapid identification of mycobacteria to the species level by polymerase chain reaction and restriction enzyme analysis

1993-02-01

Amalio Telenti , Federica Marchesi , M Balz +3 more

A method for the rapid identification of mycobacteria to the species level was developed on the basis of evaluation by the polymerase chain reaction (PCR) of the gene encoding for … A method for the rapid identification of mycobacteria to the species level was developed on the basis of evaluation by the polymerase chain reaction (PCR) of the gene encoding for the 65-kDa protein. The method involves restriction enzyme analysis of PCR products obtained with primers common to all mycobacteria. Using two restriction enzymes, BstEII and HaeIII, medically relevant and other frequent laboratory isolates were differentiated to the species or subspecies level by PCR-restriction enzyme pattern analysis. PCR-restriction enzyme pattern analysis was performed on isolates (n = 330) from solid and fluid culture media, including BACTEC, or from frozen and lyophilized stocks. The procedure does not involve hybridization steps or the use of radioactivity and can be completed within 1 working day.

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Muc2-Deficient Mice Spontaneously Develop Colitis, Indicating That MUC2 Is Critical for Colonic Protection

2006-07-01

Maria van der Sluis , Barbara A. E. de Koning , Adrianus C. J. M. de Bruijn +7 more

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Isolation and characterization of efficient plasmid transformation mutants of Mycobacterium smegmatis

1990-11-01

Scott B. Snapper , Rachel E. Melton , Shuhaimi Mustafa +2 more

Summary Recent development of vectors and methodologies to introduce recombinant DNA into members of the genus Mycobacterium has provided new approaches for investigating these important bacteria. While most pathogenic mycobacteria … Summary Recent development of vectors and methodologies to introduce recombinant DNA into members of the genus Mycobacterium has provided new approaches for investigating these important bacteria. While most pathogenic mycobacteria are slow‐growing, Mycobacterium smegmatis is a fast‐growing, non‐pathogenic species that has been used for many years as a host for mycobacteriophage propagation and, recently, as a host for the introduction of recombinant DNA. Its use as a cloning host for the analysis of mycobacterial genes has been limited by its inability to be efficiently transformed with plasmid vectors. This work describes the isolation and characterization of mutants of M. smegmatis that can be transformed, using electroporation, at efficiencies 10 4 to 10 5 times greater than those of the parent strain, yielding more than 10 5 transformants per μg of plasmid DNA. The mutations conferring this efficient plasmid transformation (Ept) phenotype do not affect phage transfection or the integration of DNA into the M. smegmatis chromosome, but seem to be specific for plasmid transformation. Such Ept mutants have been used to characterize plasmid DNA sequences essential for replication of the Mycobacterium fortuitum plasmid pAL5000 in mycobacteria by permitting the transformation of a library of hybrid plasmid constructs. Efficient plasmid transformation of M. smegmatis will facilitate the analysis of mycobacterial gene function, expression and replication and thus aid in the development of BCG as a multivalent recombinant vaccine vector and in the genetic analysis of the virulence determinants of pathogenic mycobacteria.

Polymerase Chain Reaction Amplification of a Repetitive DNA Sequence Specific for Mycobacterium tuberculosis

1990-05-01

Kathleen D. Eisenach , M. Donald Cave , Joseph H. Bates +1 more

Journal Article Polymerase Chain Reaction Amplification of a Repetitive DNA Sequence Specific for Mycobacterium tuberculosis Get access Kathleen D. Eisenach, Kathleen D. Eisenach From the Medical Research Service, McClellan Memorial … Journal Article Polymerase Chain Reaction Amplification of a Repetitive DNA Sequence Specific for Mycobacterium tuberculosis Get access Kathleen D. Eisenach, Kathleen D. Eisenach From the Medical Research Service, McClellan Memorial Veterans Hospital, and the Departments of Pathology, Anatomy, Medicine, and Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock Search for other works by this author on: Oxford Academic PubMed Google Scholar M. Donald Cave, M. Donald Cave From the Medical Research Service, McClellan Memorial Veterans Hospital, and the Departments of Pathology, Anatomy, Medicine, and Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock Search for other works by this author on: Oxford Academic PubMed Google Scholar Joseph H. Bates, Joseph H. Bates From the Medical Research Service, McClellan Memorial Veterans Hospital, and the Departments of Pathology, Anatomy, Medicine, and Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock Search for other works by this author on: Oxford Academic PubMed Google Scholar Jack T. Crawford Jack T. Crawford From the Medical Research Service, McClellan Memorial Veterans Hospital, and the Departments of Pathology, Anatomy, Medicine, and Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Infectious Diseases, Volume 161, Issue 5, May 1990, Pages 977–981, https://doi.org/10.1093/infdis/161.5.977 Published: 01 May 1990 Article history Received: 12 May 1989 Revision received: 16 November 1989 Published: 01 May 1990

Regulatory T Cell Clones Induced by Oral Tolerance: Suppression of Autoimmune Encephalomyelitis

1994-08-26

Youhai Chen , Vijay K. Kuchroo , Jun-ichi Inobe +2 more

Experimental autoimmune encephalomyelitis (EAE) is a cell-mediated autoimmune disease that serves as an animal model for multiple sclerosis. Oral administration of myelin basic protein (MBP) suppresses EAE by inducing peripheral … Experimental autoimmune encephalomyelitis (EAE) is a cell-mediated autoimmune disease that serves as an animal model for multiple sclerosis. Oral administration of myelin basic protein (MBP) suppresses EAE by inducing peripheral tolerance. T cell clones were isolated from the mesenteric lymph nodes of SJL mice that had been orally tolerized to MBP. These clones were CD4 + and were structurally identical to T helper cell type 1 (T H 1) encephalitogenic CD4 + clones in T cell receptor usage, major histocompatibility complex restriction, and epitope recognition. However, they produced transforming growth factor-β with various amounts of interleukin-4 and interleukin-10 and suppressed EAE induced with either MBP or proteolipid protein. Thus, mucosally derived T H 2-like clones induced by oral antigen can actively regulate immune responses in vivo and may represent a different subset of T cells.

Detection of rifampicin-resistance mutations in Mycobacterium tuberculosis

1993-03-01

Amalio Telenti , Paul Imboden , Federica Marchesi +6 more

The complete genome sequence ofMycobacterium bovis

2003-06-03

Thierry Garnier , Karin Eiglmeier , J.C. Camus +7 more

Mycobacterium bovis is the causative agent of tuberculosis in a range of animal species and man, with worldwide annual losses to agriculture of $3 billion. The human burden of tuberculosis … Mycobacterium bovis is the causative agent of tuberculosis in a range of animal species and man, with worldwide annual losses to agriculture of $3 billion. The human burden of tuberculosis caused by the bovine tubercle bacillus is still largely unknown. M. bovis was also the progenitor for the M. bovis bacillus Calmette–Guérin vaccine strain, the most widely used human vaccine. Here we describe the 4,345,492-bp genome sequence of M. bovis AF2122/97 and its comparison with the genomes of Mycobacterium tuberculosis and Mycobacterium leprae . Strikingly, the genome sequence of M. bovis is >99.95% identical to that of M. tuberculosis , but deletion of genetic information has led to a reduced genome size. Comparison with M. leprae reveals a number of common gene losses, suggesting the removal of functional redundancy. Cell wall components and secreted proteins show the greatest variation, indicating their potential role in host–bacillus interactions or immune evasion. Furthermore, there are no genes unique to M. bovis , implying that differential gene expression may be the key to the host tropisms of human and bovine bacilli. The genome sequence therefore offers major insight on the evolution, host preference, and pathobiology of M. bovis .

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Human T cell epitopes of Mycobacterium tuberculosis are evolutionarily hyperconserved

2010-05-23

Iñaki Comas , Jaidip Chakravartti , Peter M. Small +5 more

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Cellular and Molecular Immunology

1992-04-01

A. M. Denman

Journal Article Cellular and Molecular Immunology Get access A M Denman A M Denman Division of Immunology, Clinical Research Centre, Northwick Park Hospital, Watford Road, Harrow, Middlesex HA1 3UJ Search … Journal Article Cellular and Molecular Immunology Get access A M Denman A M Denman Division of Immunology, Clinical Research Centre, Northwick Park Hospital, Watford Road, Harrow, Middlesex HA1 3UJ Search for other works by this author on: Oxford Academic Google Scholar Postgraduate Medical Journal, Volume 68, Issue 798, April 1992, Page 305, https://doi.org/10.1136/pgmj.68.798.305 Published: 01 April 1992

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Mycobacterium abscessus: a new antibiotic nightmare

2012-01-30

Rachid Nessar , Emmanuelle Cambau , Jean‐Marc Reyrat +2 more

The intrinsic and acquired resistance of Mycobacterium abscessus to commonly used antibiotics limits the chemotherapeutic options for infections caused by these mycobacteria. Intrinsic resistance is attributed to a combination of … The intrinsic and acquired resistance of Mycobacterium abscessus to commonly used antibiotics limits the chemotherapeutic options for infections caused by these mycobacteria. Intrinsic resistance is attributed to a combination of the permeability barrier of the complex multilayer cell envelope, drug export systems, antibiotic targets with low affinity and enzymes that neutralize antibiotics in the cytoplasm. To date, acquired resistance has only been observed for aminoglycosides and macrolides, which is conferred by mutations affecting the genes encoding the antibiotic targets (rrs and rrl, respectively). Here we summarize previous and recent findings on the resistance of M. abscessus to antibiotics in light of what has been discovered for other mycobacteria. Since we can now distinguish three groups of strains belonging to M. abscessus (M. abscessus sensu stricto, Mycobacterium massiliense and Mycobacterium bolletii), studies on antibiotic susceptibility and resistance should be considered according to this new classification. This review raises the profile of this important pathogen and highlights the work needed to decipher the molecular events responsible for its extensive chemotherapeutic resistance.

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Transmission of Mycobacterium tuberculosis from patients smear-negative for acid-fast bacilli

1999-02-01

MA Behr , S. H. Warren , Hugh Salamon +4 more

Rapid Detection of Mycobacterium tuberculosis and Rifampin Resistance by Use of On-Demand, Near-Patient Technology

2009-10-29

Danica Helb , Martin Jones , Elizabeth Story‐Roller +7 more

Current nucleic acid amplification methods to detect Mycobacterium tuberculosis are complex, labor-intensive, and technically challenging. We developed and performed the first analysis of the Cepheid Gene Xpert System's MTB/RIF assay, … Current nucleic acid amplification methods to detect Mycobacterium tuberculosis are complex, labor-intensive, and technically challenging. We developed and performed the first analysis of the Cepheid Gene Xpert System's MTB/RIF assay, an integrated hands-free sputum-processing and real-time PCR system with rapid on-demand, near-patient technology, to simultaneously detect M. tuberculosis and rifampin resistance. Analytic tests of M. tuberculosis DNA demonstrated a limit of detection (LOD) of 4.5 genomes per reaction. Studies using sputum spiked with known numbers of M. tuberculosis CFU predicted a clinical LOD of 131 CFU/ml. Killing studies showed that the assay's buffer decreased M. tuberculosis viability by at least 8 logs, substantially reducing biohazards. Tests of 23 different commonly occurring rifampin resistance mutations demonstrated that all 23 (100%) would be identified as rifampin resistant. An analysis of 20 nontuberculosis mycobacteria species confirmed high assay specificity. A small clinical validation study of 107 clinical sputum samples from suspected tuberculosis cases in Vietnam detected 29/29 (100%) smear-positive culture-positive cases and 33/39 (84.6%) or 38/53 (71.7%) smear-negative culture-positive cases, as determined by growth on solid medium or on both solid and liquid media, respectively. M. tuberculosis was not detected in 25/25 (100%) of the culture-negative samples. A study of 64 smear-positive culture-positive sputa from retreatment tuberculosis cases in Uganda detected 63/64 (98.4%) culture-positive cases and 9/9 (100%) cases of rifampin resistance. Rifampin resistance was excluded in 54/55 (98.2%) susceptible cases. Specificity rose to 100% after correcting for a conventional susceptibility test error. In conclusion, this highly sensitive and simple-to-use system can detect M. tuberculosis directly from sputum in less than 2 h.

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The geographic diversity of nontuberculous mycobacteria isolated from pulmonary samples: an NTM-NET collaborative study

2013-04-18

Wouter Hoefsloot , Jakko van Ingen , Claire Andréjak +7 more

A significant knowledge gap exists concerning the geographical distribution of nontuberculous mycobacteria (NTM) isolation worldwide. To provide a snapshot of NTM species distribution, global partners in the NTM-Network European Trials … A significant knowledge gap exists concerning the geographical distribution of nontuberculous mycobacteria (NTM) isolation worldwide. To provide a snapshot of NTM species distribution, global partners in the NTM-Network European Trials Group (NET) framework ( www.ntm-net.org ), a branch of the Tuberculosis Network European Trials Group (TB-NET), provided identification results of the total number of patients in 2008 in whom NTM were isolated from pulmonary samples. From these data, we visualised the relative distribution of the different NTM found per continent and per country. We received species identification data for 20 182 patients, from 62 laboratories in 30 countries across six continents. 91 different NTM species were isolated. Mycobacterium avium complex (MAC) bacteria predominated in most countries, followed by M. gordonae and M. xenopi . Important differences in geographical distribution of MAC species as well as M. xenopi, M. kansasii and rapid-growing mycobacteria were observed. This snapshot demonstrates that the species distribution among NTM isolates from pulmonary specimens in the year 2008 differed by continent and differed by country within these continents. These differences in species distribution may partly determine the frequency and manifestations of pulmonary NTM disease in each geographical location.

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TNF Regulates Chemokine Induction Essential for Cell Recruitment, Granuloma Formation, and Clearance of Mycobacterial Infection

2002-05-01

Daniel R. Roach , Andrew G. D. Bean , Caroline Demangel +3 more

Abstract Host immunity to mycobacterial infection is dependent on the activation of T lymphocytes and their recruitment with monocytes to form granulomas. These discrete foci of activated macrophages and lymphocytes … Abstract Host immunity to mycobacterial infection is dependent on the activation of T lymphocytes and their recruitment with monocytes to form granulomas. These discrete foci of activated macrophages and lymphocytes provide a microenvironment for containing the infection. The cytokine, TNF, is essential for the formation and maintenance of granulomas, but the mechanisms by which TNF regulates these processes are unclear. We have compared the responses of TNF-deficient (TNF−/−) and wild-type C57BL/6 mice to infection with Mycobacterium smegmatis, a potent inducer of TNF, and virulent Mycobacterium tuberculosis to delineate the TNF-dependent and -independent components of the process. The initial clearance of M. smegmatis was TNF independent, but TNF was required for the early expression of mRNA encoding C-C and C-X-C chemokines and the initial recruitment of CD11b+ macrophages and CD4+ T cells to the liver during the second week of infection. Late chemokine expression and cell recruitment developed in TNF−/− mice associated with enhanced Th1-like T cell responses and mycobacterial clearance, but recruited leukocytes did not form tight granulomas. Infection of TNF−/− mice with M. tuberculosis also resulted in an initial delay in chemokine induction and cellular recruitment to the liver. Subsequently, increased mRNA expression was evident in TNF−/− mice, but the loosely associated lymphocytes and macrophages failed to form granulomas and prevent progressive infection. Therefore, TNF orchestrates early induction of chemokines and initial leukocyte recruitment, but has an additional role in the aggregation of leukocytes into functional granulomas capable of controlling virulent mycobacterial infection.

Granulomatous Infectious Diseases Associated with Tumor Necrosis Factor Antagonists

2004-04-20

Robert S. Wallis , Michael S. Broder , Jia Yi Karen Wong +2 more

The relationship between the use of tumor necrosis factor antagonists and onset of granulomatous infection was examined using data collected through the Adverse Event Reporting System of the US Food … The relationship between the use of tumor necrosis factor antagonists and onset of granulomatous infection was examined using data collected through the Adverse Event Reporting System of the US Food and Drug Administration for January 1998–September 2002. Granulomatous infections were reported at rates of ∼239 per 100,000 patients who received infliximab and ∼74 per 100,000 patients who received etanercept (P < .001). Tuberculosis was the most frequently reported disease, occurring in ∼144 and ∼35 per 100,000 infliximab-treated and etanercept-treated patients, respectively (P < .001). Candidiasis, coccidioidomycosis, histoplasmosis, listeriosis, nocardiosis, and infections due to nontuberculous mycobacteria were reported with significantly greater frequency among infliximab-treated patients. Seventy-two percent of these infection occurred ⩽90 days after starting infliximab treatment, and 28% occurred after starting etanercept treatment (P < .001). These data indicate a risk of granulomatous infection that was 3.25-fold greater among patients who received infliximab than among those who received etanercept. The clustering of reports shortly after initiation of treatment with infliximab is consistent with reactivation of latent infection.

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Executive Summary: 2013 IDSA Clinical Practice Guideline for Vaccination of the Immunocompromised Host

2014-01-13

Lorry G. Rubin , Myron J. Levin , Per Ljungman +7 more

Abstract An international panel of experts prepared an evidenced-based guideline for vaccination of immunocompromised adults and children. These guidelines are intended for use by primary care and subspecialty providers who … Abstract An international panel of experts prepared an evidenced-based guideline for vaccination of immunocompromised adults and children. These guidelines are intended for use by primary care and subspecialty providers who care for immunocompromised patients. Evidence was often limited. Areas that warrant future investigation are highlighted.

Microplate alamar blue assay versus BACTEC 460 system for high-throughput screening of compounds against Mycobacterium tuberculosis and Mycobacterium avium

1997-05-01

L A Collins , Scott G. Franzblau

In response to the need for rapid, inexpensive, high-throughput assays for antimycobacterial drug screening, a microplate-based assay which uses Alamar blue reagent for determination of growth was evaluated. MICs of … In response to the need for rapid, inexpensive, high-throughput assays for antimycobacterial drug screening, a microplate-based assay which uses Alamar blue reagent for determination of growth was evaluated. MICs of 30 antimicrobial agents against Mycobacterium tuberculosis H37Rv, M. tuberculosis H37Ra, and Mycobacterium avium were determined in the microplate Alamar blue assay (MABA) with both visual and fluorometric readings and compared to MICs determined in the BACTEC 460 system. For all three mycobacterial strains, there was < or = 1 dilution difference between MABA and BACTEC median MICs in four replicate experiments for 25 to 27 of the 30 antimicrobics. Significant differences between MABA and BACTEC MICs were observed with 0, 2, and 5 of 30 antimicrobial agents against H37Rv, H37Ra, and M. avium, respectively. Overall, MICs determined either visually or fluorometrically in MABA were highly correlated with those determined in the BACTEC 460 system, and visual MABA and fluorometric MABA MICs were highly correlated. MICs of rifampin, rifabutin, minocycline, and clarithromycin were consistently lower for H37Ra compared to H37Rv in all assays but were similar for most other drugs. M. tuberculosis H37Ra may be a suitable surrogate for the more virulent H37Rv strain in primary screening of compounds for antituberculosis activity. MABA is sensitive, rapid, inexpensive, and nonradiometric and offers the potential for screening, with or without analytical instrumentation, large numbers of antimicrobial compounds against slow-growing mycobacteria.

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Genes required for mycobacterial growth defined by high density mutagenesis

2003-03-25

Christopher M. Sassetti , Dana Boyd , Eric J. Rubin

Summary Despite over a century of research, tuberculosis remains a leading cause of infectious death worldwide. Faced with increasing rates of drug resistance, the identification of genes that are required … Summary Despite over a century of research, tuberculosis remains a leading cause of infectious death worldwide. Faced with increasing rates of drug resistance, the identification of genes that are required for the growth of this organism should provide new targets for the design of antimycobacterial agents. Here, we describe the use of transposon site hybridization (TraSH) to comprehensively identify the genes required by the causative agent, Mycobacterium tuberculosis , for optimal growth. These genes include those that can be assigned to essential pathways as well as many of unknown function. The genes important for the growth of M. tuberculosis are largely conserved in the degenerate genome of the leprosy bacillus, Mycobacterium leprae , indicating that non‐essential functions have been selectively lost since this bacterium diverged from other mycobacteria. In contrast, a surprisingly high proportion of these genes lack identifiable orthologues in other bacteria, suggesting that the minimal gene set required for survival varies greatly between organisms with different evolutionary histories.

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Impact of 16S rRNA Gene Sequence Analysis for Identification of Bacteria on Clinical Microbiology and Infectious Diseases

2004-10-01

Jill E. Clarridge

SUMMARY The traditional identification of bacteria on the basis of phenotypic characteristics is generally not as accurate as identification based on genotypic methods. Comparison of the bacterial 16S rRNA gene … SUMMARY The traditional identification of bacteria on the basis of phenotypic characteristics is generally not as accurate as identification based on genotypic methods. Comparison of the bacterial 16S rRNA gene sequence has emerged as a preferred genetic technique. 16S rRNA gene sequence analysis can better identify poorly described, rarely isolated, or phenotypically aberrant strains, can be routinely used for identification of mycobacteria, and can lead to the recognition of novel pathogens and noncultured bacteria. Problems remain in that the sequences in some databases are not accurate, there is no consensus quantitative definition of genus or species based on 16S rRNA gene sequence data, the proliferation of species names based on minimal genetic and phenotypic differences raises communication difficulties, and microheterogeneity in 16S rRNA gene sequence within a species is common. Despite its accuracy, 16S rRNA gene sequence analysis lacks widespread use beyond the large and reference laboratories because of technical and cost considerations. Thus, a future challenge is to translate information from 16S rRNA gene sequencing into convenient biochemical testing schemes, making the accuracy of the genotypic identification available to the smaller and routine clinical microbiology laboratories.

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Impairment of Mycobacterial Immunity in Human Interleukin-12 Receptor Deficiency

1998-05-29

Frédéric Altare , Anne Durandy , David A. Lammas +7 more

In humans, interferon gamma (IFN-gamma) receptor deficiency leads to a predisposition to mycobacterial infections and impairs the formation of mature granulomas. Interleukin-12 (IL-12) receptor deficiency was found in otherwise healthy … In humans, interferon gamma (IFN-gamma) receptor deficiency leads to a predisposition to mycobacterial infections and impairs the formation of mature granulomas. Interleukin-12 (IL-12) receptor deficiency was found in otherwise healthy individuals with mycobacterial infections. Mature granulomas were seen, surrounded by T cells and centered with epithelioid and multinucleated giant cells, yet reduced IFN-gamma concentrations were found to be secreted by activated natural killer and T cells. Thus, IL-12-dependent IFN-gamma secretion in humans seems essential in the control of mycobacterial infections, despite the formation of mature granulomas due to IL-12-independent IFN-gamma secretion.

THE ENVELOPE OF MYCOBACTERIA

1995-06-01

Patrick J. Brennan , Hiroshi Nikaido

Mycobacteria, members of which cause tuberculosis and leprosy, produce cell walls of unusually low permeability, which contribute to their resistance to therapeutic agents. Their cell walls contain large amounts of … Mycobacteria, members of which cause tuberculosis and leprosy, produce cell walls of unusually low permeability, which contribute to their resistance to therapeutic agents. Their cell walls contain large amounts of C 60 -C 90 fatty acids, mycolic acids, that are covalently linked to arabinogalactan. Recent studies clarified the unusual structures of arabinogalactan as well as of extractable cell wall lipids, such as trehalose-based lipooligosaccharides, phenolic glycolipids, and glycopeptidolipids. Most of the hydrocarbon chains of these lipids assemble to produce an asymmetric bilayer of exceptional thickness. Structural considerations suggest that the fluidity is exceptionally low in the innermost part of bilayer, gradually increasing toward the outer surface. Differences in mycolic acid structure may affect the fluidity and permeability of the bilayer, and may explain the different sensitivity levels of various mycobacterial species to lipophilic inhibitors. Hydrophilic nutrients and inhibitors, in contrast, traverse the cell wall presumably through channels of recently discovered porins.

An Official ATS/IDSA Statement: Diagnosis, Treatment, and Prevention of Nontuberculous Mycobacterial Diseases

2007-02-03

David E. Griffith , Timothy R. Aksamit , Barbara A. Brown‐Elliott +7 more

Diagnostic Criteria of Nontuberculous Mycobacterial Lung Disease Key Laboratory Features of NTM Health Careand Hygiene-associated Disease Prevention Prophylaxis and Treatment of NTM Disease Introduction Methods Taxonomy Epidemiology Pathogenesis Host Defense … Diagnostic Criteria of Nontuberculous Mycobacterial Lung Disease Key Laboratory Features of NTM Health Careand Hygiene-associated Disease Prevention Prophylaxis and Treatment of NTM Disease Introduction Methods Taxonomy Epidemiology Pathogenesis Host Defense and Immune Defects Pulmonary Disease Body Morphotype Tumor Necrosis Factor Inhibition Laboratory Procedures Collection, Digestion, Decontamination, and Staining of Specimens Respiratory Specimens Body Fluids, Abscesses, and Tissues Blood Specimen Processing Smear Microscopy Culture Techniques Incubation of NTM Cultures NTM Identification Antimicrobial Susceptibility Testing for NTM Molecular Typing Methods of NTM Clinical Presentations and Diagnostic Criteria Pulmonary Disease Cystic Fibrosis Hypersensitivity-like Disease Transplant Recipients Disseminated Disease Lymphatic Disease Skin, Soft Tissue, and Bone Disease

Clinical and Taxonomic Status of Pathogenic Nonpigmented or Late-Pigmenting Rapidly Growing Mycobacteria

2002-10-01

Barbara A. Brown‐Elliott , Richard J. Wallace

SUMMARY The history, taxonomy, geographic distribution, clinical disease, and therapy of the pathogenic nonpigmented or late-pigmenting rapidly growing mycobacteria (RGM) are reviewed. Community-acquired disease and health care-associated disease are highlighted … SUMMARY The history, taxonomy, geographic distribution, clinical disease, and therapy of the pathogenic nonpigmented or late-pigmenting rapidly growing mycobacteria (RGM) are reviewed. Community-acquired disease and health care-associated disease are highlighted for each species. The latter grouping includes health care-associated outbreaks and pseudo-outbreaks as well as sporadic disease cases. Treatment recommendations for each species and type of disease are also described. Special emphasis is on the Mycobacterium fortuitum group, including M. fortuitum, M. peregrinum, and the unnamed third biovariant complex with its recent taxonomic changes and newly recognized species (including M. septicum, M. mageritense, and proposed species M. houstonense and M. bonickei). The clinical and taxonomic status of M. chelonae, M. abscessus, and M. mucogenicum is also detailed, along with that of the closely related new species, M. immunogenum. Additionally, newly recognized species, M. wolinskyi and M. goodii, as well as M. smegmatis sensu stricto, are included in a discussion of the M. smegmatis group. Laboratory diagnosis of RGM using phenotypic methods such as biochemical testing and high-performance liquid chromatography and molecular methods of diagnosis are also discussed. The latter includes PCR-restriction fragment length polymorphism analysis, hybridization, ribotyping, and sequence analysis. Susceptibility testing and antibiotic susceptibility patterns of the RGM are also annotated, along with the current recommendations from the National Committee for Clinical Laboratory Standards (NCCLS) for mycobacterial susceptibility testing.

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IL-17 Production Is Dominated by γδ T Cells rather than CD4 T Cells during Mycobacterium tuberculosis Infection

2006-10-01

Euan Lockhart , Angela M. Green , JoAnne L. Flynn

IL-17 is a cytokine produced by T cells in response to IL-23. Recent data support a new subset of CD4 Th cells distinct from Th1 or Th2 cells that produce … IL-17 is a cytokine produced by T cells in response to IL-23. Recent data support a new subset of CD4 Th cells distinct from Th1 or Th2 cells that produce IL-17 and may contribute to inflammation. In this study, we demonstrate that, in naive mice, as well as during Mycobacterium tuberculosis infection, IL-17 production is primarily from gammadelta T cells and other non-CD4(+)CD8(+) cells, rather than CD4 T cells. The production of IL-17 by these cells is stimulated by IL-23 alone, and strongly induced by the cytokines, including IL-23, produced by M. tuberculosis-infected dendritic cells. IL-23 is present in the lungs early in infection and the IL-17-producing cells, such as gammadelta T cells, may represent a central innate protective response to pulmonary infection.

Severe Mycobacterial and Salmonella Infections in Interleukin-12 Receptor-Deficient Patients

1998-05-29

Rolien de Jong , Frédéric Altare , Inez-Anne Haagen +7 more

Interleukin-12 (IL-12) is a cytokine that promotes cell-mediated immunity to intracellular pathogens by inducing type 1 helper T cell (T H 1) responses and interferon-γ (IFN-γ) production. IL-12 binds to … Interleukin-12 (IL-12) is a cytokine that promotes cell-mediated immunity to intracellular pathogens by inducing type 1 helper T cell (T H 1) responses and interferon-γ (IFN-γ) production. IL-12 binds to high-affinity β1/β2 heterodimeric IL-12 receptor (IL-12R) complexes on T cell and natural killer cells. Three unrelated individuals with severe, idiopathic mycobacterial and S almonella infections were found to lack IL-12Rβ1 chain expression. Their cells were deficient in IL-12R signaling and IFN-γ production, and their remaining T cell responses were independent of endogenous IL-12. IL-12Rβ1 sequence analysis revealed genetic mutations that resulted in premature stop codons in the extracellular domain. The lack of IL-12Rβ1 expression results in a human immunodeficiency and shows the essential role of IL-12 in resistance to infections due to intracellular bacteria.

A Mutation in the Interferon-γ –Receptor Gene and Susceptibility to Mycobacterial Infection

1996-12-26

Melanie J. Newport , Clare Huxley , Sara Huston +4 more

Genetic differences in immune responses may affect susceptibility to mycobacterial infection, but no specific genes have been implicated in humans. We studied four children who had an unexplained genetic susceptibility … Genetic differences in immune responses may affect susceptibility to mycobacterial infection, but no specific genes have been implicated in humans. We studied four children who had an unexplained genetic susceptibility to mycobacterial infection and who appeared to have inherited the same recessive mutation from a common ancestor.

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Determination of bacterial load by real-time PCR using a broad-range (universal) probe and primers set

2002-01-01

Mangala A. Nadkarni , F. Elizabeth Martin , Nicholas A. Jacques +1 more

The design and evaluation of a set of universal primers and probe for the amplification of 16S rDNA from the Domain Bacteria to estimate total bacterial load by real-time PCR … The design and evaluation of a set of universal primers and probe for the amplification of 16S rDNA from the Domain Bacteria to estimate total bacterial load by real-time PCR is reported. Broad specificity of the universal detection system was confirmed by testing DNA isolated from 34 bacterial species encompassing most of the groups of bacteria outlined in Bergey's Manual of Determinative Bacteriology. However, the nature of the chromosomal DNA used as a standard was critical. A DNA standard representing those bacteria most likely to predominate in a given habitat was important for a more accurate determination of total bacterial load due to variations in 16S rDNA copy number and the effect of generation time of the bacteria on this number, since rapid growth could result in multiple replication forks and hence, in effect, more than one copy of portions of the chromosome. The validity of applying these caveats to estimating bacterial load was confirmed by enumerating the number of bacteria in an artificial sample mixed in vitro and in clinical carious dentine samples. Taking these parameters into account, the number of anaerobic bacteria estimated by the universal probe and primers set in carious dentine was 40-fold greater than the total bacterial load detected by culture methods, demonstrating the utility of real-time PCR in the analysis of this environment.

Sequence-based identification of microbial pathogens: a reconsideration of Koch's postulates

1996-01-01

Doral Fredericks , David A. Relman

Over 100 years ago, Robert Koch introduced his ideas about how to prove a causal relationship between a microorganism and a disease. Koch's postulates created a scientific standard for causal … Over 100 years ago, Robert Koch introduced his ideas about how to prove a causal relationship between a microorganism and a disease. Koch's postulates created a scientific standard for causal evidence that established the credibility of microbes as pathogens and led to the development of modern microbiology. In more recent times, Koch's postulates have evolved to accommodate a broader understanding of the host-parasite relationship as well as experimental advances. Techniques such as in situ hybridization, PCR, and representational difference analysis reveal previously uncharacterized, fastidious or uncultivated, microbial pathogens that resist the application of Koch's original postulates, but they also provide new approaches for proving disease causation. In particular, the increasing reliance on sequence-based methods for microbial identification requires a reassessment of the original postulates and the rationale that guided Koch and later revisionists. Recent investigations of Whipple's disease, human ehrlichiosis, hepatitis C, hantavirus pulmonary syndrome, and Kaposi's sarcoma illustrate some of these issues. A set of molecular guidelines for establishing disease causation with sequence-based technology is proposed, and the importance of the scientific concordance of evidence in supporting causal associations is emphasized.

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Massive gene decay in the leprosy bacillus

2001-02-01

Stewart T. Cole , Karin Eiglmeier , Julian Parkhill +7 more

Proposal for Standardization of Optimized Mycobacterial Interspersed Repetitive Unit-Variable-Number Tandem Repeat Typing ofMycobacterium tuberculosis

2006-12-01

Philip Supply , Caroline Allix , Sarah Lesjean +7 more

Molecular typing based on 12 loci containing variable numbers of tandem repeats of mycobacterial interspersed repetitive units (MIRU-VNTRs) has been adopted in combination with spoligotyping as the basis for large-scale, … Molecular typing based on 12 loci containing variable numbers of tandem repeats of mycobacterial interspersed repetitive units (MIRU-VNTRs) has been adopted in combination with spoligotyping as the basis for large-scale, high-throughput genotyping of Mycobacterium tuberculosis. However, even the combination of these two methods is still less discriminatory than IS6110 fingerprinting. Here, we define an optimized set of MIRU-VNTR loci with a significantly higher discriminatory power. The resolution and the stability/robustness of 29 loci were analyzed, using a total of 824 tubercle bacillus isolates, including representatives of the main lineages identified worldwide so far. Five loci were excluded for lack of robustness and/or stability in serial isolates or isolates from epidemiologically linked patients. The use of the 24 remaining loci increased the number of types by 40%--and by 23% in combination with spoligotyping--among isolates from cosmopolitan origins, compared to those obtained with the original set of 12 loci. Consequently, the clustering rate was decreased by fourfold--by threefold in combination with spoligotyping--under the same conditions. A discriminatory subset of 15 loci with the highest evolutionary rates was then defined that concentrated 96% of the total resolution obtained with the full 24-locus set. Its predictive value for evaluating M. tuberculosis transmission was found to be equal to that of IS6110 restriction fragment length polymorphism typing, as shown in a companion population-based study. This 15-locus system is therefore proposed as the new standard for routine epidemiological discrimination of M. tuberculosis isolates and the 24-locus system as a high-resolution tool for phylogenetic studies.

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Diagnosis and Treatment of Disease Caused by Nontuberculous Mycobacteria

1990-10-01

Richard J. Wallace , Richard O’Brien , Jeffrey Glassroth +2 more

Diagnostic Criteria of Nontuberculous Mycobacterial Lung Disease For patients with a cavitary infiltrate: Two or more sputums or bronchial washings that are acid-fast bacilli smear positive and/or produce moderate to … Diagnostic Criteria of Nontuberculous Mycobacterial Lung Disease For patients with a cavitary infiltrate: Two or more sputums or bronchial washings that are acid-fast bacilli smear positive and/or produce moderate to heavy growth on culture.Exclusion of other reasonable causes for the disease.II. For patients with a noncavitary infiltrate: Two or more sputums or bronchial washings that are acid-fast bacilli smear positive and/or produce moderate to heavy growth on culture.The isolate is Mycobacterium avium complex or M. kansasii and cannot be cleared from the sputum with either bronchial hygiene or 2 wk of drug therapy.Exclusion of other reasonable causes for the disease.For patients with a cavitary or noncavitary infiltrate whose sputum evaluations are nondiagnostic or another disease cannot be excluded: 1. Lung biopsy yields a NTM.2. The biopsy shows mycobacterial histopathologic features (i.e., granulomatous inflammation) and two or more sputums are positive for a NTM even in low numbers.

Genetic Dissection of Immunity to Mycobacteria: The Human Model

2002-04-01

Jean‐Laurent Casanova , Laurent Abel

Humans are exposed to a variety of environmental mycobacteria (EM), and most children are inoculated with live Bacille Calmette-Guérin (BCG) vaccine. In addition, most of the world's population is occasionally … Humans are exposed to a variety of environmental mycobacteria (EM), and most children are inoculated with live Bacille Calmette-Guérin (BCG) vaccine. In addition, most of the world's population is occasionally exposed to human-borne mycobacterial species, which are less abundant but more virulent. Although rarely pathogenic, mildly virulent mycobacteria, including BCG and most EM, may cause a variety of clinical diseases. Mycobacterium tuberculosis, M. leprae, and EM M. ulcerans are more virulent, causing tuberculosis, leprosy, and Buruli ulcer, respectively. Remarkably, only a minority of individuals develop clinical disease, even if infected with virulent mycobacteria. The interindividual variability of clinical outcome is thought to result in part from variability in the human genes that control host defense. In this well-defined microbiological and clinical context, the principles of mouse immunology and the methods of human genetics can be combined to facilitate the genetic dissection of immunity to mycobacteria. The natural infections are unique to the human model, not being found in any of the animal models of experimental infection. We review current genetic knowledge concerning the simple and complex inheritance of predisposition to mycobacterial diseases in humans. Rare patients with Mendelian disorders have been found to be vulnerable to BCG, a few EM, and M. tuberculosis. Most cases of presumed Mendelian susceptibility to these and other mycobacterial species remain unexplained. In the general population leprosy and tuberculosis have been shown to be associated with certain human genetic polymorphisms and linked to certain chromosomal regions. The causal vulnerability genes themselves have yet to be identified and their pathogenic alleles immunologically validated. The studies carried out to date have been fruitful, initiating the genetic dissection of protective immunity against a variety of mycobacterial species in natural conditions of infection. The human model has potential uses beyond the study of mycobacterial infections and may well become a model of choice for the investigation of immunity to infectious agents.

Nontuberculous mycobacteria and associated diseases.

1979-12-01

Jr. William H. Oatway

Epidemiology of infection by nontuberculous mycobacteria

1996-04-01

J O Falkinham

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Infection withMycobacterium aviumComplex in Patients without Predisposing Conditions

1989-09-28

David Prince , Donald D. Peterson , Robert M. Steiner +5 more

Pulmonary disease caused by Mycobacterium avium complex usually occurs in patients with chronic lung disease or deficient cellular immunity, and its prevalence is increasing. We describe 21 patients (mean age, … Pulmonary disease caused by Mycobacterium avium complex usually occurs in patients with chronic lung disease or deficient cellular immunity, and its prevalence is increasing. We describe 21 patients (mean age, 66 years) with such infection without the usual predisposing factors, representing 18 percent of the 119 patients surveyed. Seventeen women and 4 men were given a diagnosis of M. avium complex from 1978 to 1987, with a stable incidence over the decade, on the basis of pulmonary symptoms, abnormalities on chest films, positive cultures, and in 14, biopsy evidence of invasive disease. Most of the patients (86 percent) presented with persistent cough and purulent sputum, usually without fever or weight loss. The cough was present for a mean of 25 weeks before the correct diagnosis was made. Radiographic patterns of slowly progressive nodular opacities predominated (71 percent); only five patients had cavitary disease at presentation. All patients responded initially to antimycobacterial therapy, but eight eventually relapsed when it was stopped. Four patients died of progressive pulmonary infection caused by M. avium complex. The extent of the initial pulmonary involvement was greater in patients with progressive disease than in those whose condition improved. We conclude that pulmonary disease caused by the M. avium complex can affect persons without predisposing conditions, particularly elderly women, and that recognition of this disease is often delayed because of its indolent nature.

An expansion of rare lineage intestinal microbes characterizes rheumatoid arthritis

2016-04-21

Jun Chen , Kerry Wright , John M. Davis +6 more

The adaptive immune response in rheumatoid arthritis (RA) is influenced by an interaction between host genetics and environment, particularly the host microbiome. Association of the gut microbiota with various diseases … The adaptive immune response in rheumatoid arthritis (RA) is influenced by an interaction between host genetics and environment, particularly the host microbiome. Association of the gut microbiota with various diseases has been reported, though the specific components of the microbiota that affect the host response leading to disease remain unknown. However, there is limited information on the role of gut microbiota in RA. In this study we aimed to define a microbial and metabolite profile that could predict disease status. In addition, we aimed to generate a humanized model of arthritis to confirm the RA-associated microbe. To identify an RA biomarker profile, the 16S ribosomal DNA of fecal samples from RA patients, first-degree relatives (to rule out environment/background as confounding factors), and random healthy non-RA controls were sequenced. Analysis of metabolites and their association with specific taxa was performed to investigate a potential mechanistic link. The role of an RA-associated microbe was confirmed using a human epithelial cell line and a humanized mouse model of arthritis. Patients with RA exhibited decreased gut microbial diversity compared with controls, which correlated with disease duration and autoantibody levels. A taxon-level analysis suggested an expansion of rare taxa, Actinobacteria, with a decrease in abundant taxa in patients with RA compared with controls. Prediction models based on the random forests algorithm suggested that three genera, Collinsella, Eggerthella, and Faecalibacterium, segregated with RA. The abundance of Collinsella correlated strongly with high levels of alpha-aminoadipic acid and asparagine as well as production of the proinflammatory cytokine IL-17A. A role for Collinsella in altering gut permeability and disease severity was confirmed in experimental arthritis. These observations suggest dysbiosis in RA patients resulting from the abundance of certain rare bacterial lineages. A correlation between the intestinal microbiota and metabolic signatures could determine a predictive profile for disease causation and progression.

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Mycobacterium aviumComplex Infection in the Acquired Immunodeficiency Syndrome

1991-05-09

C. Robert Horsburgh

ORGANISMS of the Mycobacterium avium complex have long been recognized as an uncommon cause of pneumonia in persons with chronic lung disease.1 2 3 4 Organisms of this complex, which … ORGANISMS of the Mycobacterium avium complex have long been recognized as an uncommon cause of pneumonia in persons with chronic lung disease.1 2 3 4 Organisms of this complex, which comprises two closely related species, M. avium and M. intracellulare, appear to have little virulence in the normal host. Before the acquired immunodeficiency syndrome (AIDS) epidemic, disseminated infection with M. avium complex was extremely rare; by 1980, only 24 cases had been reported in the medical literature.5 Beginning in 1982, however, when the infection was recognized in patients with AIDS, the number of cases increased dramatically.At first, the minimal inflammatory response . . .

Anonymous Mycobacteria in Pulmonary Disease

1959-01-01

Ernest H. Runyon

Type VII secretion — mycobacteria show the way

2007-10-08

Abdallah M. Abdallah , Nicolaas C. Gey van Pittius , Patricia A. Champion +5 more

A Rapid One-Step Trichrome Stain*

1950-07-01

George Gömöri

A Rapid One-Step Trichrome Stain* George GoMori, M.D. George GoMori, M.D. From the Department of Medicine, The University of Chicago, Chicago, Illinois Search for other works by this author on: … A Rapid One-Step Trichrome Stain* George GoMori, M.D. George GoMori, M.D. From the Department of Medicine, The University of Chicago, Chicago, Illinois Search for other works by this author on: Oxford Academic Google Scholar *This work has been done under grants from the Douglas Smith Foundation for Medical Research of the University of Chicago and from the Pathology Study section of the United States Public Health Service. Author Notes American Journal of Clinical Pathology, Volume 20, Issue 7_ts, July 1950, Pages 661–664, https://doi.org/10.1093/ajcp/20.7_ts.661 Published: 01 July 1950 Article history Received: 01 December 1949 Published: 01 July 1950

Phylogenomics and Comparative Genomic Studies Robustly Support Division of the Genus Mycobacterium into an Emended Genus Mycobacterium and Four Novel Genera

2018-02-13

Radhey S. Gupta , Brian Lo , Jeen Son

The genus Mycobacterium contains 188 species including several major human pathogens as well as numerous other environmental species. We report here comprehensive phylogenomics and comparative genomic analyses on 150 genomes … The genus Mycobacterium contains 188 species including several major human pathogens as well as numerous other environmental species. We report here comprehensive phylogenomics and comparative genomic analyses on 150 genomes of Mycobacterium species to understand their interrelationships. Phylogenetic trees were constructed for the 150 species based on 1941 core proteins for the genus Mycobacterium, 136 core proteins for the phylum Actinobacteria and 8 other conserved proteins. Additionally, the overall genome similarity amongst the Mycobacterium species was determined based on average amino acid identity of the conserved protein families. The results from these analyses consistently support the existence of five distinct monophyletic groups within the genus Mycobacterium at the highest level, which are designated as the "Tuberculosis-Simiae," "Terrae," "Triviale," "Fortuitum-Vaccae," and "Abscessus-Chelonae" clades. Some of these clades have also been observed in earlier phylogenetic studies. Of these clades, the "Abscessus-Chelonae" clade forms the deepest branching lineage and does not form a monophyletic grouping with the "Fortuitum-Vaccae" clade of fast-growing species. In parallel, our comparative analyses of proteins from mycobacterial genomes have identified 172 molecular signatures in the form of conserved signature indels and conserved signature proteins, which are uniquely shared by either all Mycobacterium species or by members of the five identified clades. The identified molecular signatures (or synapomorphies) provide strong independent evidence for the monophyly of the genus Mycobacterium and the five described clades and they provide reliable means for the demarcation of these clades and for their diagnostics. Based on the results of our comprehensive phylogenomic analyses and numerous identified molecular signatures, which consistently and strongly support the division of known mycobacterial species into the five described clades, we propose here division of the genus Mycobacterium into an emended genus Mycobacterium encompassing the "Tuberculosis-Simiae" clade, which includes all of the major human pathogens, and four novel genera viz. Mycolicibacterium gen. nov., Mycolicibacter gen. nov., Mycolicibacillus gen. nov. and Mycobacteroides gen. nov. corresponding to the "Fortuitum-Vaccae," "Terrae," "Triviale," and "Abscessus-Chelonae" clades, respectively. With the division of mycobacterial species into these five distinct groups, attention can now be focused on unique genetic and molecular characteristics that differentiate members of these groups.

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Diagnosis and Treatment of Disease Caused by Nontuberculous Mycobacteria

1997-08-01

Diagnostic criteria of nontuberculous mycobacterial lung disease in HIV-seropositive and -seronegative hosts. The following criteria apply to symptomatic patients with infiltrate, nodular or cavitary disease, or a high resolution computed … Diagnostic criteria of nontuberculous mycobacterial lung disease in HIV-seropositive and -seronegative hosts. The following criteria apply to symptomatic patients with infiltrate, nodular or cavitary disease, or a high resolution computed tomography scan that shows multifocal bronchiectasis and/or multiple small nodules. A. If three sputum/bronchial wash results are available from the previous 12 mo: 1. three positive cultures with negative AFB smear results or 2. two positive cultures and one positive AFB smear B. If only one bronchial wash is available: 1. positive culture with a 2+, 3+, or 4+ AFB smear or 2+, 3+, or 4+ growth on solid media C. If sputum/bronchial wash evaluations are nondiagnostic or another disease cannot be excluded: 1. transbronchial or lung biopsy yielding a NTM or 2. biopsy showing mycobacterial histopathologic features (granulomatous inflammation and/or AFB) and one or more sputums or bronchial washings are positive for an NTM even in low numbers.these criteria fit best with M. avium complex, M. abscessus, and M. kansasii. Too little is known of other NTM to be certain how applicable these criteria will be. At least three respiratory samples should be evaluated from each patient. Other reasonable causes for the disease should be excluded. Expert consultation should be sought when diagnostic difficulties are encountered.

Diagnostic Standards and Classification of Tuberculosis in Adults and Children

2000-04-01

Identification of Mycobacterium Species by DNA Microarray Chip Method

2025-06-24

Zixuan Chen , Jianming Zhang , Yancheng Jiang +2 more | Journal of Visualized Experiments

Recent advances in mycobacterial transcription: insights beyond the general pathway

2025-06-24

Nilanjana Hazra , Jayanta Mukhopadhyay | Journal of Bacteriology

The conventional idea of prokaryotic transcription represents a collection of pathways assembled from disparate studies across diverse bacterial species. This cumulative approach, though reveals core-conserved mechanisms, likely excludes the transcriptional … The conventional idea of prokaryotic transcription represents a collection of pathways assembled from disparate studies across diverse bacterial species. This cumulative approach, though reveals core-conserved mechanisms, likely excludes the transcriptional pathways unique to an organism. The understanding of mycobacterial transcription suffers from such generalizations as its extreme GC bias, complex RNA polymerase (RNAP), abundance of short transcripts predominating its transcriptome, extensive σ factor utilization, and a constant battle against host stress implicates a distinct transcriptional landscape. This review highlights specific insights into mycobacterial RNAP architecture, promoter recognition, and elongation dynamics, against the general comprehensive narration of bacterial transcription.

Draft genome of Staphylococcus epidermidis clinical isolate OGSA-Sep-145 from an implant-related spinal infection

2025-06-24

Vincenzo Pennone , Matteo Briguglio , Elena De Vecchi +2 more | Microbiology Resource Announcements

Staphylococcus epidermidis, a skin commensal, is a major cause of orthopedic implant-related infections due to its biofilm-forming ability and immune evasion strategies. Here, we present the draft genome of strain … Staphylococcus epidermidis, a skin commensal, is a major cause of orthopedic implant-related infections due to its biofilm-forming ability and immune evasion strategies. Here, we present the draft genome of strain OGSA-Sep-145, isolated from a spinal infection, providing insights into antimicrobial resistance and virulence mechanisms in chronic infections.

A case of polyserositis with pericarditis caused by Mycobacterium spp.

2025-06-24

Filipa Figueiredo , Teresa Valido , Jéssica Oliveira +4 more | European Journal of Case Reports in Internal Medicine

The incidence of diseases and deaths caused by non-tuberculous mycobacteria (NTM) has been increasing globally. However, the broad and nonspecific clinical manifestations of NTM infections make diagnosis challenging, compounded by … The incidence of diseases and deaths caused by non-tuberculous mycobacteria (NTM) has been increasing globally. However, the broad and nonspecific clinical manifestations of NTM infections make diagnosis challenging, compounded by the difficulty in isolating NTM organisms. While NTM are rarely associated with heart disease, including pericarditis, and pleural effusion, such presentations are exceptional. We report the case of an 85-year-old female who presented with polyserositis, characterized by pleural and pericardial effusion, and was diagnosed with an unusual manifestation of NTM infection causing pericarditis. Initially, the patient was misdiagnosed with tuberculosis, which delayed the correct diagnosis and appropriate treatment. Upon accurate diagnosis, her condition improved with adjustments to the treatment regimen. This case highlights the importance of considering NTM infection in the differential diagnosis, particularly when faced with atypical presentations. Early recognition and timely microbiological testing are crucial for accurate diagnosis, enabling targeted treatment and improving patient outcomes.

Draft genome sequence of Mycobacterium avium complex isolated from a patient with sepsis in Thailand

2025-06-23

Panuwat Sathianpitayakul , Takeshi Komine , Panan Ratthawongjirakul +3 more | Microbiology Resource Announcements

We report the draft genome sequence of Mycobacterium avium complex isolate cultured from the blood of a patient in Thailand. Genomic features analysis indicates that this strain represents a distinct … We report the draft genome sequence of Mycobacterium avium complex isolate cultured from the blood of a patient in Thailand. Genomic features analysis indicates that this strain represents a distinct taxon within the MAC group.

Comparative Analysis of Several Detection Methods for Mycobacterium Tuberculosis in Paraffin-Embedded Tissues

2025-06-23

Tao-Hua Liu , Xirun Zheng , Han Liu +3 more | Research Square (Research Square)

<title>Abstract</title> <bold>Objective:</bold> To evaluate the diagnostic value of real-time quantitative PCR (RT-qPCR) and metagenomics next-generation sequencing (mNGS) in detecting Mycobacterium tuberculosis (MTB) in paraffin-embedded tissue samples. <bold>Methods:</bold> Twenty paraffin-embedded tissue … <title>Abstract</title> <bold>Objective:</bold> To evaluate the diagnostic value of real-time quantitative PCR (RT-qPCR) and metagenomics next-generation sequencing (mNGS) in detecting Mycobacterium tuberculosis (MTB) in paraffin-embedded tissue samples. <bold>Methods:</bold> Twenty paraffin-embedded tissue samples diagnosed with chronic granulomatous inflammation were selected. RT-qPCR and mNGS were performed on these samples, and Ziehl-Neelsen acid-fast staining was conducted for comparison. <bold>Results:</bold> Among the 20 specimens, 10 cases were identified as Mycobacterium tuberculosis complex (MTBC) by both RT-qPCR and mNGS, with a concordance rate of 100%. Acid-fast staining results differed from both molecular methods in four samples. Among the 10 RT-qPCR-negative samples, mNGS detected no mycobacteria in 6 cases, while non-tuberculous mycobacteria (NTM) were identified in 4 cases (including Mycobacterium wolinskyi, Mycobacterium gallinarum, and Mycobacterium kansasii). Acid-fast staining results differed from mNGS in one sample. <bold>Conclusion:</bold> Compared to acid-fast staining, RT-qPCR demonstrated higher sensitivity in detecting MTBC and can be used as a routine tool for rapid detection of MTB DNA in paraffin-embedded tissues. mNGS, when economically feasible, can serve as an important method for detecting non-tuberculous mycobacteria or other pathogens.

Current Status of Diagnostic Tests for Hematologic Neoplasms in Korea (2024)

2025-06-23

Mi‐Ae Jang , Jung Hee Yoon , Chang‐Hun Park +7 more | Laboratory Medicine Online

PMS2<scp>c.2117del</scp> (<scp>p.Lys706Serfs*19</scp>) is the Most Frequent Cancer‐Associated Founder Pathogenic Variant in the French‐Canadian Population of Quebec, Canada

2025-06-23

Anne‐Laure Chong , Alejandro Mejía‐García , Supriya Behl +7 more | Clinical Genetics

ABSTRACT We identified a PMS2 variant (NM_000535.7:c.2117del, p.Lys706Serfs*19) in 22 French‐Canadian (FC) families from Quebec with Lynch syndrome (LS; n = 21) or constitutional mismatch repair deficiency (CMMRD; n = … ABSTRACT We identified a PMS2 variant (NM_000535.7:c.2117del, p.Lys706Serfs*19) in 22 French‐Canadian (FC) families from Quebec with Lynch syndrome (LS; n = 21) or constitutional mismatch repair deficiency (CMMRD; n = 1). We aimed to (a) confirm its founder origin, (b) assess its allele frequency in the FC population, and (c) determine its contribution to the risk of developing various cancers in this population. We identified a haplotype common to all c.2117del alleles spanning 666 kb to 1.37 Mb, confirming the founder nature of the variant. In affected cases, the variant was found in 0 out of 821 breast cancer cases, 8 out of 693 (1.15%) endometrial cancer (EC) cases, and 1 out of 191 (0.52%) colorectal cancer (CRC) cases. In unaffected persons, the variant was identified in 22/6347 newborns (0.35%) and in 21/18129 FC CARTaGENE cohort participants (0.12%). Within this cohort, an excess of CRC (odds ratio: 10.7; 95% CI: 1.42–80.1; p value = 0.022), but not EC, was seen among heterozygotes for the PMS2 founder variant. Analysis of the variant in 24 subregions of Quebec showed over‐representation in 5 of them. Here, we report the most frequent genetic cause of mismatch repair deficiency syndromes identified thus far in the FC population of Quebec.

Antimycobacterial Activity of Phytochemical Extracts from Herbs against the Non-tuberculous Mycobacterium fortuitum Infecting Fish

2025-06-23

S. Gangatharan , A. Uma , K.G. Tirumurugaan +2 more | Indian Journal of Animal Research

Background: Non-tuberculous mycobacteriosis (NTM) is widespread in natural and grown edible and ornamental fish and is caused by Mycobacterium fortuitum. Mycobacterial infection in fish causes clinical signs like discoloration of … Background: Non-tuberculous mycobacteriosis (NTM) is widespread in natural and grown edible and ornamental fish and is caused by Mycobacterium fortuitum. Mycobacterial infection in fish causes clinical signs like discoloration of the skin and exposed sores affecting the commercial value of fish. Moreover, mycobacteriosis is thought as a zoonotic disease making it much worse for edible fishes. Methods: The antimycobacterial efficacy of the phytochemical extracts from Tribulus terrestris, Mimosa pudica, Leucas aspera, Foeniculum vulgare, Cinnamomum verum and Acorus calamus was studied against Mycobacterium fortuitum secluded from a diseased ornamental fish, Betta splendens. The antimycobacterial efficiency of extracts of these herbs made with water and methanol was estimated in vitro using a 96-well microplate assay technique with a Resazurin dye. Result: The aqueous and methanolic extracts of Acorus calamus, Mimosa pudica and Cinnamomum verum (50 μg/ml) exhibited the highest antimycobacterial activity after that Foeniculum vulgare and Tribulus terrestris (100 μg/ml). The least inhibition activity was exhibited by Leucas aspera (200 μg/ml). These results revealed that the extracts of Acorus calamus, Cinnamomum verum and Mimosa pudica can be used as an alternative to the present antimycobacterial drugs for the treatment of Mycobacteriosis in edible and ornamental fish. However, further studies on the active compounds involved in the antimycobacterial activities of these herbs are needed.

Thoracic magnetic resonance imaging in non-tuberculous mycobacterial pulmonary disease: Characteristics and potential implementation

2025-06-23

Ieuan Evans , Timothy Baird , Charles Haworth +7 more | PLoS ONE

Non-tuberculous mycobacteria (NTM) are pulmonary pathogens with increasing incidence and prevalence worldwide, with people with cystic fibrosis (pwCF) traditionally considered at high risk of disease development. The imaging assessment of … Non-tuberculous mycobacteria (NTM) are pulmonary pathogens with increasing incidence and prevalence worldwide, with people with cystic fibrosis (pwCF) traditionally considered at high risk of disease development. The imaging assessment of NTM-pulmonary disease (NTM-PD) relies heavily on high-resolution computed tomography (HRCT). However, due to lengthy treatment regimens and the need for long-term follow-up, serial HRCT's result in progressive exposure to ionizing radiation; a particular concern in younger people. We performed a retrospective cohort study of patients who had undergone serial thoracic magnetic resonance imaging (tMRI) scans to monitor NTM-PD as a novel tool to image the lung with a view to creating an algorithm for the utility of tMRI in the management of NTM-PD. Thirty-six patients, of which twenty-four had a diagnosis of CF, with suspected or confirmed NTM-PD underwent serial tMRI between 1st January 2013 and 30th June 2018. A total of 117 serial tMRI's were performed (mean number per patient 3.25; range 2-6). The associated clinical impact that each serial MRI had on management, deemed as the utility of tMRI, found that all tMRI's were classified as aiding management with 60 (51.3%) altering management. tMRI's were more likely to alter management in the non-CF cohort than the CF cohort (69.4% vs. 43.2%). No imaging-related adverse events were reported across the 117 tMRI's. This study highlights that tMRI may hold promise as a monitoring tool in NTM-PD and should be prospectively evaluated in the monitoring of individuals with NTM-PD.

Structures of MmpL complexes reveal the assembly and mechanism of this family of transporters

2025-06-22

Zhemin Zhang , Rakesh Maharjan , William D. Gregor +2 more | bioRxiv (Cold Spring Harbor Laboratory)

We co-expressed the MmpL5 transporter and MmpS5 adaptor proteins in Mycobacterium smegmatis and defined their structures from these detergent-solubilized crude membranes. Data generated from these samples allowed us to simultaneously … We co-expressed the MmpL5 transporter and MmpS5 adaptor proteins in Mycobacterium smegmatis and defined their structures from these detergent-solubilized crude membranes. Data generated from these samples allowed us to simultaneously solve three distinct classes of membrane protein complexes to high resolutions. We observed that MmpL5 presents as a monomer in complex with the cytosolic meromycolate extension acyl carrier protein M (AcpM) in a molar ratio of 1:1, where these AcpM-MmpL5 complexes closely pack together to generate regular two-dimensional arrays. We also identified MmpL5 as a trimer that interacts with MmpS5 and AcpM in a molar ratio of 3:3:3 to assemble the tripartite complex AcpM-MmpL5-MmpS5 that spans both the inner and outer membranes of the mycobacterium. In addition, we discovered that MmpL5 and AcpM are able to form the trimeric AcpM-MmpL5 complex in a molar ratio of 3:3. The structural data reveal that the full-length MmpL5 trimer is capable of spanning the entire mycobacterial cell envelope to transport substrates. However, this assembly requires the presence of MmpS5 to stabilize secondary structural features of the MmpL5 periplasmic subdomains.

Influence of Paratuberculosis Vaccination on the Local Immune Response in Experimentally Infected Calves: An Immunohistochemical Analysis

2025-06-22

David Zapico , José Espinosa , M. Muñoz +4 more | Animals

Vaccination remains the most cost-effective way to control clinical paratuberculosis in dairy herds, but its effect on the immune response at the intestine have been poorly characterized. The aim of … Vaccination remains the most cost-effective way to control clinical paratuberculosis in dairy herds, but its effect on the immune response at the intestine have been poorly characterized. The aim of this study was to evaluate the expression of toll-like receptor (TLR)-1, TLR2, TLR4, TLR9, interferon (IFN)-γ, inducible nitric oxide synthase (iNOS) and cluster of differentiation (CD)-204 in calves vaccinated with Silirum® and then experimentally infected with paratuberculosis, using immunohistochemical techniques. Samples of the injection-site granuloma, scapular lymph node, intestine and mesenteric lymph nodes were studied. Lesions were classified as focal, multifocal and diffuse paucibacillary (lymphocytic). The immunolabeling for TLR1, TLR2, TLR4 and IFN-γ was assessed according to the number of immunolabeled cells, while TLR9, iNOS and CD204 immunolabeling in the lesions was evaluated using a histological score (H-score). Vaccinated calves with focal forms showed a significant increase in the number of macrophages immunolabeled TLR2 at the intestine and in the H-score values for iNOS in the granulomas. A greater immunolabeling of TLR2 and IFN-γ was detected at the injection-site granuloma. Animals with multifocal lesions, regardless of the vaccination status, showed lower numbers of TLR2+ macrophages and higher H-score values for CD204 in the granulomas. Thus, the protection conferred by the Silirum® vaccine is associated with an enhanced immunological response in the intestine.

Mycophenolic-acid

2025-06-21

| Reactions Weekly

VLX600, an anticancer iron chelator, exerts antimicrobial effects on Mycobacterium abscessus infections

2025-06-20

Jaehun Oh , Seaone Choi , Hyejun Seo +7 more | Microbiology Spectrum

ABSTRACT Mycobacterium abscessus presents significant clinical challenges due to its intrinsic and acquired resistance to antibiotics, resulting in prolonged treatments and poor patient outcomes. Addressing the urgent need for novel … ABSTRACT Mycobacterium abscessus presents significant clinical challenges due to its intrinsic and acquired resistance to antibiotics, resulting in prolonged treatments and poor patient outcomes. Addressing the urgent need for novel therapeutics, this study explores the antimicrobial potential of VLX600, originally developed as an anticancer agent, against M. abscessus . Screening a library of 3,200 clinically evaluated compounds identified VLX600 as a potent antimicrobial with minimal cytotoxicity. VLX600 demonstrated inhibitory effects against various strains of M. abscessus with minimum inhibitory concentrations of 4 µg/mL–16 µg/mL. It also remained effective in intracellular M. abscessus in host cells and exhibited broad-spectrum activity against other bacterial species, including Escherichia coli , Staphylococcus aureus , and Pseudomonas aeruginosa . The antimicrobial activity of VLX600 was abrogated by supplemental iron, indicating a mechanism dependent on iron chelation. VLX600 significantly reduced bacterial burdens and inflammation in a murine model of pulmonary M. abscessus infection. Additionally, synergistic effects were observed when VLX600 was combined with conventional antibiotics such as amikacin and clarithromycin in vitro . These findings highlight VLX600 as a promising candidate for repurposing as an antimicrobial agent against M. abscessus , warranting further clinical investigations. IMPORTANCE Mycobacterium abscessus is an opportunistic pathogen that commonly causes pulmonary infections in cystic fibrosis patients. These infections are notoriously difficult to treat due to high levels of antibiotic resistance of M. abscessus , resulting in low cure rates. In this study, we identified a novel antibiotic candidate, VLX600, through high-throughput screening of 3,200 clinical compounds and demonstrated that VLX600 inhibits the growth of M. abscessus by depriving it of ferric and ferrous ions. This study highlights the potential of iron chelators as antimicrobial agents against M. abscessus infections. Since iron is an essential nutrient for the growth of many bacteria, the use of iron chelators could be extended to other infectious diseases. We hope this research will inspire further studies aimed at developing iron chelators as a novel class of antimicrobial agents.

Üst Ekstremitede Yerleşen Nadir Görülen bir Lupus Vulgaris Vakası

2025-06-20

Dündar Can Dündar , Engin Şenel , Muhammed Enes Gürbüz +1 more | Dicle Medical Journal / Dicle Tip Dergisi

Tüberküloz (TB), Mycobacterium tuberculosis bakterisinin neden olduğu ve kronik granülomatöz inflamatuar yanıtla seyreden önemli bir enfeksiyon hastalığıdır. Deri TB, diğer organlarla karşılaştırıldığında oldukça seyrek rastlanan bir patolojidir. Dermatoloji polikliniklerine başvuran … Tüberküloz (TB), Mycobacterium tuberculosis bakterisinin neden olduğu ve kronik granülomatöz inflamatuar yanıtla seyreden önemli bir enfeksiyon hastalığıdır. Deri TB, diğer organlarla karşılaştırıldığında oldukça seyrek rastlanan bir patolojidir. Dermatoloji polikliniklerine başvuran bireylerde, deri TB görülme oranının %0,1 ile %0,5 arasında değiştiği farklı çalışmalarda belirtilmiştir.Deri TB'nin etken patojenleri arasında M. tuberculosis, M. bovis ve nadiren BCG aşısının atenüe suşu yer almaktadır. En yaygın deri TB tipi olan Lupus vulgaris (LV), kronik ve ilerleyici bir form olup, genellikle daha önce TB basiline maruz kalmış duyarlı bireylerde gelişir. LV'nin tanısı klinik bulgular ve histopatolojik incelemelerle konulmakta olup, tedavisi dörtlü antitüberküloz rejimi ile yapılmaktadır. Bu çalışmada, yirmi yıl önce sağ el bileğinde küçük bir papül olarak başlayan ve büyüyen lezyon nedeniyle başvuran bir LV vakası sunulmaktadır. Hastaya yapılan biyopsi sonucu LV tanısı konulmuş ve altı aylık tedavi sonrası lezyonlarda gerileme gözlemlenmiştir. Deri TB'nin nadir bir formu olan LV, genellikle baş ve boyun bölgesinde görülürken, bu olgu nadir tutulum olarak el bileğinde tespit edilmiştir. Deri TB'nin erken tanı ve tedavisi, komplikasyonların önlenmesi açısından büyük önem taşımaktadır.

Biomarker discovery for non-invasive diagnosis of inflammatory bowel disease using blood transcriptomics

2025-06-20

Mohammad Hossein Derakhshan Nazari , Mahsa Ghorbaninejad , Shabnam Shahrokh +1 more | Frontiers in Immunology

Introduction Colonoscopy remains the gold standard for diagnosing inflammatory bowel disease (IBD) even though it is an invasive and costly procedure. To enable non-invasive diagnosis, we aimed to identify blood-based … Introduction Colonoscopy remains the gold standard for diagnosing inflammatory bowel disease (IBD) even though it is an invasive and costly procedure. To enable non-invasive diagnosis, we aimed to identify blood-based transcriptomic biomarkers that specifically distinguish IBD from healthy and inflammatory controls. Methods Public microarray and RNA-seq datasets from whole blood of IBD, rheumatoid arthritis (RA), and control subjects were analyzed. RA was included as a positive control for systemic inflammation to filter out non-IBD-specific gene signatures. Differentially expressed genes (DEGs) were identified, followed by immune cell deconvolution (CIBERSORTx), pathway and network analysis, and diagnostic model construction using LASSO and SVM. A real-life cohort (36 IBD patients, 30 controls) was recruited for qRT-PCR validation. Results IBD blood transcriptomes exhibited altered immune profiles, including increased M0 macrophages, Tregs, and CD4 naïve T cells, and decreased memory B and activated NK cells. After excluding RA-overlapping DEGs, 25 IBD-specific DEGs with |log2FC| &gt; 0.5 were prioritized. LASSO and SVM identified a three-mRNA panel—IL4R, EIF5A, and SLC9A8—which achieved 84% diagnostic accuracy in the discovery cohort and 99% accuracy in the real-life cohort. Network analysis highlighted NDUFB2 as a key downregulated hub gene linked to mitochondrial complex I dysfunction and oxidative phosphorylation disruption. Elevated oxidative stress in IBD was confirmed by increased Total Oxidant Status (TOS) levels in patient plasma. Discussion Our findings support the use of peripheral blood transcriptomics for IBD diagnosis and demonstrate that a focused three-gene panel can achieve high diagnostic accuracy. The inclusion of RA as an inflammatory control enabled the identification of IBD-specific markers, minimizing confounding from general immune activation. These results provide a practical foundation for developing non-invasive diagnostic tools for clinical use.

An overview of Quorum sensing in Mycobacterium tuberculosis, tuberculosis and diabetes mellitus

2025-06-20

Shireen Adeeb Mujtaba Ali | Reviews in Medical Microbiology

Every 15 s, a person worldwide dies due to tuberculosis (TB), a disease brought on by Mycobacterium tuberculosis (M. tb). One of the basic mechanisms by which bacteria impose collective … Every 15 s, a person worldwide dies due to tuberculosis (TB), a disease brought on by Mycobacterium tuberculosis (M. tb). One of the basic mechanisms by which bacteria impose collective behaviors is cell-to-cell communication called Quorum sensing mechanism (QSM). Patients with cystic fibrosis have frequently had sputum samples containing a wide genetic variety of mycobacteria. Due to minute modifications in their morphology, distributive conjugal transfer (DCT), and gene expression level, heterogenic mycobacterial populations are seen to arise. India became a focal point of the global tuberculosis (TB) crisis. The nation, which in 2020 reported the greatest number of projected incident cases of tuberculosis (1.5 million among a total predicted 5.8 million worldwide cases), has set an aggressive goal to eradicate tuberculosis by 2025, as opposed to the traditional deadline of 2030. According to estimates, India will have the second-highest number of diabetes cases worldwide in 2021 (74 million out of an anticipated 537 million cases). It has been highlighted that diabetes treatment, a significant comorbidity among TB patients, should be handled in tandem with TB treatment since early detection is likely to save patient expenditures. In the present review article, authors have given an overview on Quorum sensing in M. tb, Quorum sensing mechanism in M. tb and correlation between TB and diabetes mellitus (DM).

Comparative study of Chinese herbal enema combined with Mesalazine versus Mesalazine alone in the treatment of ulcerative colitis: A randomized controlled trial

2025-06-19

Jiao Zhang , Bin Shi , Da Li +5 more | Journal of the Chinese Medical Association

Background: Mesalazine is a standard treatment for ulcerative colitis (UC). However, it is unclear whether the efficacy of mesalazine combined with traditional Chinese medicine (TCM) enemas is superior to that … Background: Mesalazine is a standard treatment for ulcerative colitis (UC). However, it is unclear whether the efficacy of mesalazine combined with traditional Chinese medicine (TCM) enemas is superior to that of mesalazine alone. Therefore, this study aimed to evaluate the clinical effectiveness of TCM enema hydrotherapy combined with mesalazine for active UC. Methods: Patients with active UC were randomly assigned to two treatment groups: a combination of mesalazine and TCM enemas and mesalazine alone. Outcome measures included TCM symptom scores, levels of inflammatory markerss [interleukin-8 (IL-8), tumor necrosis factor α (TNF-α), high-sensitivity C-reactive protein (hs-CRP)], colonoscopy scores (Baron score), disease activity indices [Sutherland Disease Activity Index (DAI), modified Mayo score], and recurrence rates. Results: A total of 80 patients were included in the study. Regarding the primary outcomes, the total effective rate in the combination group was 95%, which was significantly higher than the 75% observed in the mesalazine group ( p < 0.05). The recurrence rate was lower in the combined group (2.5%) than in the mesalazine group (17.5%) ( p < 0.05). Regarding secondary outcomes, the combination group showed higher reductions in TCM symptom scores than the mesalazine group, particularly in the areas of bloody stool, diarrhea, and abdominal pain ( p < 0.05). The combined group also showed significantly lower inflammatory markers (IL-8, TNF-α, hs-CRP) and disease activity scores (Baron score, DAI, modified Mayo score) compared to the mesalazine group ( p < 0.05). Conclusion: The combination of TCM enema hydrotherapy and mesalazine therapy led to significant clinical improvement with lower inflammatory responses and reduced recurrence rates in patients with active UC. The combination treatment may be more effective than mesalazine alone and shows promise as a management option for UC.

Intracellular glutamine fluctuates with nitrogen availability and regulatesMycobacterium smegmatisbiofilm formation

2025-06-19

Elizabeth B. Varner , Mitchell D. Meyer , Joe Whalen +6 more | bioRxiv (Cold Spring Harbor Laboratory)

Abstract Biofilm formation allows pathogenic nontuberculous mycobacteria (NTM) to adhere to household plumbing systems and has been observed in vivo during human infection. Glucose drives NTM aggregation in vitro , … Abstract Biofilm formation allows pathogenic nontuberculous mycobacteria (NTM) to adhere to household plumbing systems and has been observed in vivo during human infection. Glucose drives NTM aggregation in vitro , and ammonium inhibits it, but the regulatory systems controlling this early step in biofilm formation are not understood. Here, we show that a variety of carbon and nitrogen sources have similar impacts on aggregation in the model NTM Mycobacterium smegmatis as glucose and ammonium, suggesting that the response to these nutrients is general and likely sensed through downstream, integrated signals. Next, we performed a transposon screen in M. smegmatis to uncover these putative regulatory nodes. Our screen revealed that mutating specific genes in the purine and pyrimidine biosynthesis pathways caused an aggregation defect, but supplementing with adenosine and guanosine had no impact on aggregation either in a purF mutant or WT. Realizing that the only genes we hit in purine or pyrimidine biosynthesis were those that utilized glutamine as a nitrogen donor, we pivoted to the hypothesis that intracellular glutamine could be a nitrogen-responsive node affecting aggregation. We tested this hypothesis in defined M63 medium using targeted mass spectrometry. Indeed, intracellular glutamine increased with nitrogen availability and correlated with planktonic growth. Furthermore, a garA mutant, which has an artificially expanded glutamine pool in growth phase, grew solely as planktonic cells even without nitrogen supplementation. Altogether these results establish that intracellular glutamine controls M. smegmatis aggregation, and they introduce flux-dependent sensors as key components of the NTM biofilm regulatory system. Importance A subset of nontuberculous mycobacteria (NTM), including Mycobacterium abscessus , are opportunistic pathogens that can cause severe pulmonary infections. M. abscessus is present in showerhead biofilms, one of the reservoirs from which it can infect susceptible individuals. Moreover, M. abscessus can exist as biofilms during pulmonary infections, and biofilm formation in vitro renders M. abscessus more tolerant to antibiotics. The ability to inhibit NTM biofilm formation could therefore help us better prevent and treat NTM infections. However, the regulatory systems controlling NTM biofilm formation, which could include targets for anti-biofilm therapeutics, are poorly understood. The significance of this work is that it reveals intracellular glutamine as an important node controlling initiation of biofilm formation in the model NTM Mycobacterium smegmatis . Building on this foundation, future studies will investigate how NTM biofilms can be dispersed by altering glutamine levels and will describe how NTM translates intracellular glutamine to alteration of surface adhesins.

Metagenomic sequencing for identification of nontuberculous mycobacteria and other pathogens in patients with mixed infection of the lung

2025-06-19

Jinyan Yu , Xuejiao Lv , Qi Wang +2 more | Frontiers in Cellular and Infection Microbiology

Background It can be difficult to distinguish lung disease caused by nontuberculous mycobacteria (NTM), Mycobacterium tuberculosis , and mixed infections (MIs) that include NTM. Metagenomic next generation sequencing (mNGS) is … Background It can be difficult to distinguish lung disease caused by nontuberculous mycobacteria (NTM), Mycobacterium tuberculosis , and mixed infections (MIs) that include NTM. Metagenomic next generation sequencing (mNGS) is a highly sensitive method that can reliably identify lung pathogens. We retrospectively analyzed the records of patients who had MIs of the lungs that included NTM and received mNGS testing. Methods The records of 36 patients who were diagnosed with NTM infection of the lungs at the Second Hospital of Jilin University from Nov 2023 to Jun 2024 were analyzed. Initial empirical treatments were ineffective in all patients, leading to the application of mNGS of bronchoalveolar lavage fluid (BALF). Results The average patient age was 62.4 years, 22 patients had one or more underlying chronic disease, and all patients had at least one respiratory symptom (cough, sputum production, fever, or dyspnea). Chest CT examinations showed that patients had different degrees of pneumonia and pleural effusion. Among tested patients, there were elevated levels of erythrocyte sedimentation rate in 81.8% (18/22) and elevated C-reactive protein in 90.5% (19/21). There were variable results from acid-fast staining of bronchoalveolar lavage fluid (BALF; 3/36, 8.3%), and transbronchial lung biopsy (TBLB; 5/14, 35.7%). mNGS identified seven NTM species. Treatment based on the mNGS results led to the resolution of clinical symptoms and absorption of lung lesions in all patients. Conclusions Most of the 36 patients with MIs of the lungs that included NTM had underlying diseases. The results of traditional tests, including sputum or BALF culture and smear, acute phase markers, and TBLB pathological examination, were problematic. mNGS provides rapid and reliable diagnosis, allowing the rapid implementation of appropriate therapy in patients with MIs of the lungs that include NTM.

When is the best time to test paratuberculosis positivity? Observations from a follow-up study in Hungarian dairy herds

2025-06-19

Barbara Vass-Bognár , Mikolt Bakony , Kinga Fornyos +3 more | Frontiers in Veterinary Science

The objective of the present study was to find the most practical combination of diagnostic procedures and time points during lactation to identify Mycobacterium avium ssp. paratuberculosis (MAP)-infected animals. Four … The objective of the present study was to find the most practical combination of diagnostic procedures and time points during lactation to identify Mycobacterium avium ssp. paratuberculosis (MAP)-infected animals. Four Hungarian dairy farms with a 4–5% apparent MAP positivity were enrolled in the study, and 13 non-lactating, known MAP-positive pregnant cows were chosen from each farm. Feces, blood, and milk samples were collected from each cow at 1–5, 10–14, 40–60, 90–120, 180–200, and 280–300 days in milk (DIM) and ELISA and PCR assays were performed for antibody or pathogen detection. Animals that later developed clinical paratuberculosis symptoms showed distinctly different patterns of test positivity than those that did not develop clinical symptoms during the observation period. The optimal time for detecting MAP-positive animals with the highest probability was DIM 40–60 with serum ELISA and DIM 10–14 and 40–60 for PCR assays, respectively. Serum ELISA proved to be slightly more sensitive than milk ELISA. S/P values showed a moderate correlation with the fecal qPCR Ct values. We found that the most suitable period for MAP screening is 40–60 days after calving.

Erratum for Singh et al., “Repurposing drugs to advance the treatment of Buruli ulcer”

2025-06-18

Sanjay Singh , Rie Yotsu , Eric L. Nuermberger +1 more | Antimicrobial Agents and Chemotherapy

Medication adherence in patients with nontuberculous mycobacterial disease

2025-06-18

Arthur Lemson , Fleur Dijkhuizen , Ralf Stemkens +5 more | Journal of Clinical Tuberculosis and Other Mycobacterial Diseases

Atypical Nontuberculous Mycobacterium Infection Following Body Contouring Implants

2025-06-18

Thapasvi Anantha , Robert S Houser , Casey T. Kraft | Aesthetic Plastic Surgery

Investigating the Impact of the Gut Microbiota on Nasal Polyp Development: Insights from Mendelian Randomization

2025-06-18

Ning Lü , Yuxu Yao , Meiling Gao +4 more | International Archives of Allergy and Immunology

Background: Chronic rhinosinusitis with nasal polyps has a high post-surgery recurrence, suggesting complex pathology. However, research into underlying mechanisms and contributing factors, such as gut microbiota, is lacking. Objective: We … Background: Chronic rhinosinusitis with nasal polyps has a high post-surgery recurrence, suggesting complex pathology. However, research into underlying mechanisms and contributing factors, such as gut microbiota, is lacking. Objective: We investigated the cause-and-effect relationship between nasal polyps and the gut microbiota and determined the influence of metabolic pathways as possible mediators. Methods: This study utilized genetic data from genome-wide association studies. The datasets included nasal polyp data from FinnGen (6,841 cases and 308,457 control samples), microbial metabolic pathway data from the Dutch Microbiome Project (7,738 samples), and single nucleotide polymorphisms of the gut microbiota from MiBioGen (18,340 samples). First, two-sample Mendelian randomization (MR) analyses were conducted on the gut microbiota, nasal polyps, and metabolic pathways. Next, a two-step MR was employed for mediation analysis to investigate whether metabolic pathways serve as mediators between the gut microbiota and nasal polyps and to estimate the proportion of the effect of metabolism-mediated gut microbiota on nasal polyps. Results: MR analysis revealed that Alcaligenaceae was associated with a higher risk of nasal polyps by inhibiting enopyranuronate degradation, whereas Desulfovibrionales had the opposite effect by promoting l-isoleucine biosynthesis. In addition, Actinomyces reduced the risk of nasal polyps by inhibiting L-glutamate degradation but also increased the risk by inhibiting sulfate reduction. Conclusion: This study identified a causal relationship between the gut microbiota and nasal polyps, with metabolic pathways as mediators. Our study provides new perspectives and possibilities for the study and treatment of chronic rhinosinusitis with nasal polyps.

Mycoplasma-related acute hemorrhagic leukoencephalomyelitis

2025-06-18

Mathias Fousse , Jakob Stögbauer , Michael Kettner | Deutsches Ärzteblatt international

Potential Microorganisms from Bronchial Lavage Fluid in Bronchiectasis Patients: Bacteria, Nontuberculous Mycobacteria, and Fungi

2025-06-18

Lam Nguyen‐Ho , Quoc‐Khanh Tran‐Le , Tu Trinh +7 more | The Open Respiratory Medicine Journal

Introduction Bronchiectasis is a chronic lung disease characterized by irreversible bronchial dilation, often accompanied by persistent infections. Compared to sputum, the microbiological results of bronchial lavage fluid (BLF) from stable … Introduction Bronchiectasis is a chronic lung disease characterized by irreversible bronchial dilation, often accompanied by persistent infections. Compared to sputum, the microbiological results of bronchial lavage fluid (BLF) from stable bronchiectasis patients are typically less explored. There is emerging evidence on the role of non-tuberculous mycobacteria (NTM) in the progression of bronchiectasis. This study aims to investigate the microbiological profiles of BLF and the rate of NTM detection in stable bronchiectasis patients. Methods We conducted a prospective observational multicenter study at two endoscopy units of Cho Ray’s Hospital and University Medical Center Ho Chi Minh City, from January 2023 to February 2024. Adult patients with bronchiectasis who underwent bronchoscopy were enrolled, and the BLF was collected. The BLF samples were analyzed for bacterial and fungal pathogens using culture methods, and for NTM using the multiplex polymerase chain reaction (PCR) technique. Results Of the 112 initially assessed patients, 99 were eligible for this study. The mean age was 63 years, and 55.6% were female. Bacterial cultures were positive in 41.9% of cases (36/86), predominantly with isolates of Klebsiella pneumoniae and Pseudomonas aeruginosa . Multi-drug resistant (MDR) K. pneumoniae and Acinetobacter baumannii were notably detected. Using PCR, NTM was detected in 52.5% of patients (52/99), predominantly slow-growing species such as Mycobacterium xenopi and Mycobacterium avium-intracellulare complex. Fungal cultures were positive in 24.6% of cases (17/69), primarily involving Candida spp. and Aspergillus spp. Patients with higher bronchiectasis severity index had higher rates of positive bacterial culture, but lower rates of NTM detection. Conclusion This study demonstrated a microbial diversity in BLF, notably NTM and MDR bacteria in Vietnamese patients with bronchiectasis, emphasizing the need for routine, comprehensive microbial assessment for bronchiectasis patients. The incorporation of advanced molecular techniques can improve the detection of NTM in these patients.

Abdominal Wall Abscess Caused by Tsukamurella tyrosinosolvens Misdiagnosed as Tuberculosis: A Case Report

2025-06-17

Yudan Zhang , Zhenghua Wu , Tianyu Zhou +4 more | SN Comprehensive Clinical Medicine

Use of plant extracts against rapidly growing mycobacteria: a review

2025-06-17

Maiara Oliveira Jantsch , Marli Matiko Anraku de Campos | Brazilian Journal of Health Review

Nontuberculous mycobacteria comprise a diverse group of environmental microorganisms, among which Rapidly Growing Mycobacteria (RGM) have stood out for their ability to cause opportunistic infections, especially following invasive procedures. The … Nontuberculous mycobacteria comprise a diverse group of environmental microorganisms, among which Rapidly Growing Mycobacteria (RGM) have stood out for their ability to cause opportunistic infections, especially following invasive procedures. The increasing resistance of these species to conventional antimicrobials, combined with their capacity to form biofilms, underscores the urgent need for new therapeutic alternatives. Among these, natural products have shown promise, particularly plant extracts, due to their phytochemical complexity and potential synergistic action. Accordingly, this study aims to conduct a review of the scientific literature on plant extracts evaluated in vitro against RGM species. The search in PubMed, Scopus, and Science Direct databases resulted in 35 articles, of which 11 met the eligibility criteria. Notably, the genus Searsia was the most frequently cited; South Africa was the country with the highest number of plant collections; and leaves were the most commonly used plant part. Acetone was the most employed solvent, and Mycolicibacterium fortuitum was the most frequently tested species. The results indicated a significant variety of plants with antimycobacterial potential, reinforcing the importance of biodiversity as a source of bioactive compounds. Although preliminary, the findings of this review lay a foundation for further, more in-depth investigations into the use of plant extracts in controlling RGM infections.

Spatiotemporal distribution of Mycobacterium ulcerans and other Mycolactone Producing Mycobacteria in Southeastern United States

2025-06-17

Magdalene Dogbe , Cody Roberts , Kayla M. Fast +7 more | Emerging Microbes & Infections

Buruli ulcer (BU) is a chronic and debilitating skin disease caused by the environmental pathogen, Mycobacterium ulcerans (MU). The primary virulence determinant is mycolactone, a cytotoxic lipid compound unique to … Buruli ulcer (BU) is a chronic and debilitating skin disease caused by the environmental pathogen, Mycobacterium ulcerans (MU). The primary virulence determinant is mycolactone, a cytotoxic lipid compound unique to MU and its other mycolactone producing mycobacteria (MPM) ecological variants. Although BU prevalence is highest in West Africa and Australia, little is known about MU and other MPM distribution in non-endemic regions such as the Southeastern United States (US). In this study, environmental samples (water filtrand, plant biofilm, soil, aquatic invertebrates) were collected from nine freshwater sites across Louisiana, Mississippi and Alabama over three sampling periods (August 2020, November 2020, March 2021). Samples were screened for MU and MPM presence and abundance by PCR and genotyped using variable number tandem repeat (VNTR) profiling. All nine sites were positive for MU or other MPM DNA in at least one substrate, except invertebrates. Overall, mean concentrations were 4.3 × 104 genome units (GU)/sample in August 2020, 1.26 GU/sample in November 2020, and 55.5 GU/sample in March 2021. Profiling by VNTR identified four MU (designated A-D) and one M. liflandii genotype(s), among environmental samples, with genotype frequencies varying by site and sampling time. Detection of MU and M. liflandii genotypes in Southeastern US aquatic environments, matching those from BU endemic regions, provides rationale for ongoing surveillance. Our findings broaden the known geographic range of MU and MPMs and offer baseline data to help predict and prevent and predict the possibility of zoonotic transmission in Southeastern US.

The Epidemiological Characteristics and its Associated Driving Factors of Tuberculosis Among Migrant Populations in Zhejiang Province

2025-06-17

Zhengwei Liu , Jiani Miao , Rongrong Qu +7 more | Research Square (Research Square)

<title>Abstract</title> Background Population mobility exacerbates tuberculosis (TB) transmission risks. As a major immigration hub in China, Zhejiang Province has become a critical region for the importation of TB cases. This … <title>Abstract</title> Background Population mobility exacerbates tuberculosis (TB) transmission risks. As a major immigration hub in China, Zhejiang Province has become a critical region for the importation of TB cases. This study aims to explore the epidemiological characteristics of TB in Zhejiang and identify the key driving factors associated with its transmission. Methods TB surveillance data in Zhejiang Province (2005–2023) was analyzed using joinpoint regression, age-period-cohort modeling, and spatial autocorrelation to examine incidence trends and disparities between migrant and local cases. The boosted regression trees model identified the driving factors of TB among migrant populations. Results Zhejiang Province witnessed an annual average TB incidence of 61.35 per 100,000, with 34.48% migrant cases. The incidence initially increased during 2005–2007 with an annual percent change (APC) of 2.76%, followed by sustained decline thereafter (APC = -4.12%), while migrant proportions increased until 2019 (APC = 5.83%) then sharply decreased during 2019–2023 (APC = -17.62%). TB incidence exhibited bimodal age effects (peaks aged 15–19 and 80–84 years) alongside birth cohort effects showing risk reduction in the post-1974 cohorts. The incidence hot spots transitioned from Hangzhou to Quzhou, while they persisted in Quzhou and Lishui for local cases, and contrasting shifted to Ningbo and Jiaxing for migrant cases. The gross regional product (GRP) per capita (56.82%, 95%CI: 56.19–57.44), tertiary industry proportion (8.98%, 95%CI: 8.66–9.27) and emigration index (7.38%, 95%CI: 7.16–7.67) were identified as the primary driving factors of TB among migrant populations. Conclusions Although a sustained decline in TB incidence was observed among the local population in Zhejiang, migrant proportions demonstrated steady growth. The incidence hot spots showed divergent patterns between migrant and local case. GRP per capita, tertiary industry proportion, and emigration index serve as primary driving factors for TB among migrant populations, which guide targeted strategies among origin-specific migrant populations to reduce TB transmission.

Single-Sample Melt-Based Screening for Rifampicin Susceptibility in the Emerging Mutation Hotspot at rpoB Codon 491

2025-06-17

Nicole A. Malofsky , Swayashreyee B. Dhungel , Megan E. Pask +1 more | ACS Infectious Diseases

Based on sequencing data, mutations at rpoB codon 491 ofMycobacterium tuberculosisare associated with rifampicin resistance, but current commercial and WHO-endorsed genotypic tests fail to detect them. As a result, resistant … Based on sequencing data, mutations at rpoB codon 491 ofMycobacterium tuberculosisare associated with rifampicin resistance, but current commercial and WHO-endorsed genotypic tests fail to detect them. As a result, resistant infections go untreated, driving transmission and multidrug resistance. A real-time PCR assay by André et al. specifically screens for I491F but omits other codon 491 mutations. To address this gap, a single-sample screening method using asymmetric PCR followed by melt analysis was developed for the three sequence-identified variants, I491F/N/M. Each sample contained a melt probe matching the susceptible sequence, which, after asymmetric PCR spanning codon 491, hybridized with the excess strand to form a duplex. The duplex's melt temperature (Tm) was then measured. To enable single-sample classification, each reaction also included double-stranded L-DNA identical to the probe and wild-type PCR product duplex. Susceptibility was determined by the within-sample Tm difference between the probe-product and L-DNA duplexes. The approach was evaluated and compared to the André assay across two calibrated PCR instruments using synthetic rpoB wild-type and variant sequences. As expected, the André assay distinguished wild-type from I491F samples but misclassified I491N and I491M samples based on multisample Tm comparison. In contrast, our single-sample classification strategy used within-sample Tm differences, classifying samples as rifampicin-susceptible when the within-sample Tm difference was less than 0.83 °C. With this approach, the method achieved 100% sensitivity and 100% specificity across both PCR instruments. Although demonstrated for rpoB codon 491, this assay design is readily adaptable to any other sequence-identified, clinically significant mutation hotspot.

Novel C5α-substituted carbapenems enhance Mycobacterium abscessus killing via selective target binding and reduced hydrolysis by Bla Mab

2025-06-17

Eunjeong Shin , Magdalena A. Taracila , Pojun Quan +7 more | Antimicrobial Agents and Chemotherapy

ABSTRACT Mycobacterium abscessus ( Mab ) poses significant clinical challenges and underscores the urgent need for safer and more effective treatments, including β-lactams. Among currently available carbapenems, imipenem is widely … ABSTRACT Mycobacterium abscessus ( Mab ) poses significant clinical challenges and underscores the urgent need for safer and more effective treatments, including β-lactams. Among currently available carbapenems, imipenem is widely used to treat Mab infections by combining with other antibiotics. Commercial carbapenems share a common scaffold with C2 modifications, whereas this study focuses on novel carbapenem candidates with C5α modifications. We evaluated their antibacterial activity against Mab ATCC 19977 and clinical isolates, as well as their acylation of peptidoglycan target receptors (L,D-transpeptidases [LDTs] and penicillin-binding proteins [PBPs]) and the β-lactamase enzyme Bla Mab . In vitro studies of two C5α-modified carbapenems, JDB/NA-1-157 and JDB/NA-1-208, revealed distinct antibacterial effects. JDB/NA-1-157 demonstrated potent bacterial killing with low minimum inhibitory concentrations (MICs; 0.125–8 mg/L) and near-complete eradication within 5 days, surpassing the efficacy of the standard-of-care regimen (amikacin + clarithromycin + imipenem). In contrast, JDB/NA-1-208 exhibited poor bacterial killing, with high MICs (16–256 mg/L) and limited efficacy in time-kill studies. However, JDB/NA-1-208 showed synergistic killing when combined with other β-lactams. Mechanistically, JDB/NA-1-208 is not a substrate for Bla Mab , while JDB/NA-1-157 is, albeit with low catalytic efficiency. This is supported by the observation that the addition of avibactam did not enhance synergy with JDB/NA-1-157. The substantial bacterial killing effect of JDB/NA-1-157 is attributed to its high binding affinity for PBP-B, PBP-lipo, PonA2, D,D-carboxypeptidase, and LDT1–2. These findings highlight the potential of novel C5α-modified carbapenems, particularly JDB/NA-1-157, as promising therapeutic candidates for Mab infections.

Benchmarking pangenome dynamics and horizontal gene transfer in Mycobacterium marinum evolution

2025-06-17

Khandker Shahed , Sk Injamamul Islam , Papungkorn Sangsawad +3 more | Frontiers in Microbiology

Horizontal gene transfer (HGT) is a key driver of microbial evolution, promoting genetic diversity and contributing to the emergence of antibiotic resistance. This study explores the pangenome dynamics and HGT … Horizontal gene transfer (HGT) is a key driver of microbial evolution, promoting genetic diversity and contributing to the emergence of antibiotic resistance. This study explores the pangenome dynamics and HGT in Mycobacterium marinum ( M. marinum ), a close relative of Mycobacterium tuberculosis . Multiple pangenome datasets were analyzed to quantify gene gain, loss, and pangenome openness, utilizing Panstripe and a Generalized Linear Model (GLM) framework to assess gene presence/absence across strains. Additionally, a comparative benchmarking analysis of gene ontology (GO) annotations were conducted using eggNOG and InterProScan to evaluate their functional annotation accuracy. Our findings demonstrated significant differences in gene gain and loss rates, suggesting variations in annotation accuracy and the presence of mobile genetic elements (MGE). Single nucleotide polymorphisms (SNPs) were also identified, highlighting the genetic variability that may impact strain-specific traits such as pathogenicity and antibiotic resistance. Pangenome of M. marinum was characterized as highly open, with substantial variability in gene content, reflecting ongoing genetic exchange and adaptability. Functional annotation benchmarking demonstrated that eggNOG and InterProScan provided complementary insights, with each tool excelling in distinct strengths of gene function identification. Overall, these findings highlight the complex interplay between HGT, pangenome evolution, and antibiotic resistance in M. marinum , and the analytical framework presented here provides a robust approach for future studies aiming to inform therapeutic interventions and vaccine development.

Rapid Response and Containment of an NDM-Producing Klebsiella Pneumoniae Outbreak in a Hematology Ward: Case Study from an Italian Hospital

2025-06-17

Ilaria Tocco Tussardi , Giovanni Stévanin , Luca Montesarchio +5 more | Healthcare

Antimicrobial resistance (AMR) constitutes a critical threat to global public health, with carbapenem-resistant Enterobacterales (CRE) presenting significant challenges due to their resistance to last-line antibiotics. Among these, New Delhi metallo-beta-lactamase … Antimicrobial resistance (AMR) constitutes a critical threat to global public health, with carbapenem-resistant Enterobacterales (CRE) presenting significant challenges due to their resistance to last-line antibiotics. Among these, New Delhi metallo-beta-lactamase (NDM)-producing Klebsiella pneumoniae (KP) is of particular concern. This study describes an outbreak of NDM-producing KP in the hematology unit of the University Hospital of Verona, Italy. This represents the second reported hospital outbreak of this strain in Italy, and the first to occur within a hematology ward. The outbreak involved four patients, all of whom were identified through active surveillance and microbiological screening. In response, a multidisciplinary team implemented a series of infection prevention and control (IPC) measures, which included enhanced environmental cleaning, strict hand hygiene protocols, patient isolation, and the development of a tailored IPC checklist. The outbreak was effectively contained within three weeks following the identification of the last case. This outcome underscores the importance of rapid and coordinated responses to NDM-producing KP outbreaks. This case study emphasizes the necessity of robust IPC protocols, rapid intervention, and continuous staff education in mitigating the spread of multidrug-resistant pathogens in healthcare settings. It further highlights the urgent need for healthcare systems to be adequately prepared and resilient in addressing the growing threat of AMR.

Pulmonary Mycobacterium avium

2025-06-17

Liz Silverstone | Radiopaedia.org

TBpore cluster: A novel phylogenetic pipeline for tuberculosis transmission studies using nanopore next-generation sequencing data

2025-06-16

Sophie Gagnon , Emmanuelle S. Ametepe , Floriane Point +7 more | PLoS ONE

Background Molecular typing of Mycobacterium tuberculosis complex isolates enhances understanding of tuberculosis (TB) transmission dynamics, supporting public health efforts in outbreak investigations. This study aims to validate TBpore, a novel … Background Molecular typing of Mycobacterium tuberculosis complex isolates enhances understanding of tuberculosis (TB) transmission dynamics, supporting public health efforts in outbreak investigations. This study aims to validate TBpore, a novel bioinformatic pipeline for clustering TB transmission isolates using Oxford Nanopore Technology (ONT) data and comparing it against conventional Mycobacterial Interspersed Repetitive-Unit Variable Number (MIRU-VNTR) typing and Illumina sequencing. Methodology/Principal findings This retrospective case-control study included 58 clinical isolates from two TB outbreaks in Canada, previously characterized by public health investigations and MIRU-VNTR typing. DNA extraction and sequencing were performed on both Illumina and ONT platforms. Illumina data were processed using Clockwork and psdm, while Nanopore data were analyzed with TBpore. SNP distances were used to compare clustering results across methods, with clusters defined by SNP distance thresholds of ≤5 and ≤12. Both sequencing methods showed a high degree of concordance in clustering results. All isolates from the M. africanum outbreak clustered within the defined SNP thresholds, consistent with MIRU-VNTR and epidemiological data. In the M. tuberculosis outbreak, 20 out of 21 isolates clustered similarly across methods, with one exception. Within outbreak pairwise SNP distances were lower with Nanopore. Conclusion/Significance ONT sequencing and the TBpore pipeline offer an accurate alternative to Illumina technology for TB molecular epidemiology. This study suggests potential increased clustering sensitivity with Nanopore technology, warranting further validation on larger datasets with robust epidemiological metadata.

Cervical Lymphadenitis With Mycobacterium stomatepiae: Diagnostic and Management Challenges

2025-06-16

Holly Oliver , Denver Niles , Daniel C. Chelius +1 more | The Pediatric Infectious Disease Journal

Impact of sublineage diversity on intrinsic susceptibility of Beijing genotype Mycobacterium tuberculosis

2025-06-16

Haoran Li , Guyue Zhang , Zichun Ma +6 more | Annals of Clinical Microbiology and Antimicrobials

Tuberculosis (TB) remains a significant global health issue, with drug-resistant TB posing a major challenge. The genetic lineage of Mycobacterium tuberculosis (Mtb) is known to influence various aspects, including drug … Tuberculosis (TB) remains a significant global health issue, with drug-resistant TB posing a major challenge. The genetic lineage of Mycobacterium tuberculosis (Mtb) is known to influence various aspects, including drug resistance. Still, the relationship between different lineages and drug resistance levels, especially in the context of the Beijing genotype, requires further exploration. This study aimed to investigate the disparities in drug resistance among diverse lineages of Mtb. We analyzed 193 clinical isolates from drug-resistant TB patients, among them 91.2% were MDR/pre-XDR-TB. Samples were collected from patients at specific hospitals between 2014 and 2020. The isolates were subjected to smear microscopy, sputum culture, minimum inhibitory concentration (MIC) testing, and whole-genome sequencing (WGS). The MIC distributions and resistance levels of drugs like INH, AMK, RIF, EMB, and FQ were analyzed, and the association between lineages and drug resistance was determined using statistical tests. Our results showed significant differences in the MIC distributions and resistance levels of INH and AMK between lineages 2.2 and 2.3. Lineage 2.3.2 was a protective factor for high-level INH resistance, and lineage 2.3 was a protective factor for high-level AMK resistance. The L2.3.6 strain had a high proportion of high-level resistance to INH and AMK. This study provides evidence for the evolution and spread of the modern Beijing genotype of Mtb. It suggests that L2.3.6 will have the potential to become the main sublineage of tuberculosis for the spread of drug-resistant tuberculosis and the necessity of pedigree testing of drug-resistant strains in clinical treatment.

Diagnostic and Therapeutic Challenges in Bronchiectasis With Concurrent Allergic Bronchopulmonary Aspergillosis and Non-tuberculous Mycobacterial Infection: A Case Report

2025-06-16

Mohammad Abed Alhaleem , M. Shazam Hussain , Ahmed R. Ahmed +3 more | Cureus

Oxidative Stress and Apoptotic Markers in Goats Naturally Infected with Mycobacterium avium subsp. paratuberculosis

2025-06-16

Merve Öztürk , Muhammet Bahaeddi̇n Dörtbudak , Bayram Bekmez +5 more | Pathogens

Paratuberculosis, caused by Mycobacterium avium subspecies paratuberculosis (MAP), is a chronic granulomatous enteritis with significant implications for ruminant health, economic productivity, and potential zoonotic risk. This study investigated the expression … Paratuberculosis, caused by Mycobacterium avium subspecies paratuberculosis (MAP), is a chronic granulomatous enteritis with significant implications for ruminant health, economic productivity, and potential zoonotic risk. This study investigated the expression of biomarkers of oxidative stress and apoptosis in goats naturally infected with MAP, focusing on three biological matrices: serum, intestinal mucosa, and mesenteric lymph nodes. Twenty MAP-positive goats and ten healthy controls were included. Serum and tissue levels of malondialdehyde (MDA), glutathione S-transferase (GST), glutathione peroxidase (GPX), superoxide dismutase (SOD), glutathione reductase (GSR), and caspase-3 were quantitatively assessed using ELISA tests. Gross and histopathological analyses confirmed MAP infection. Infected animals showed significantly elevated serum levels of MDA and caspase-3 (p < 0.001), along with decreased antioxidant enzyme activities (GSR, GST, GPX, SOD). Tissue analysis revealed increased MDA and caspase-3 levels, particularly in the intestinal mucosa compared to mesenteric lymph nodes, suggesting localized oxidative damage and apoptosis. Conversely, antioxidant enzyme activity was higher in mesenteric lymph nodes, indicating a compensatory response and a pronounced involvement of the intestinal tract. These findings demonstrate that MAP infection induces marked oxidative stress and apoptotic processes, especially in the intestinal mucosa. The imbalance between pro-oxidant and antioxidant systems may play a key role in the pathogenesis and chronic progression of the disease. Caspase-3 and MDA, in particular, have been identified as promising diagnostic or prognostic biomarkers for MAP infection. This study highlights the importance of developing improved diagnostic tools and therapeutic strategies targeting oxidative stress pathways in paratuberculosis.

Design and synthesis of 2-amino-4-(trifluoromethyl)pyrimidine derivatives as potential Werner-dependent antiproliferative agents

2025-06-15

Chang You , S WEI , Jia Yu +7 more | Molecular Diversity

Defining the mechanism of action of the nitrofuranyl piperazine HC2210 against Mycobacterium abscessus

2025-06-14

Ifeanyichukwu E. Eke , Bassel J. Abdalla , Soledad Soverina +4 more | npj Antimicrobials and Resistance

Mycobacterium abscessus (Mab) has intrinsic resistance to diverse classes of antibiotics, making this non-tuberculous mycobacterial (NTM) infection challenging to treat. Three nitrofuranyl piperazines-HC2209, HC2210, and HC2211-were previously reported to be … Mycobacterium abscessus (Mab) has intrinsic resistance to diverse classes of antibiotics, making this non-tuberculous mycobacterial (NTM) infection challenging to treat. Three nitrofuranyl piperazines-HC2209, HC2210, and HC2211-were previously reported to be active against M. tuberculosis (Mtb). Here we report that HC2210 is also active against Mab and define its mechanisms of action. HC2210 is about fivefold more potent than amikacin, is active against multidrug-resistant Mab clinical isolates, and synergizes with bedaquiline, clarithromycin, and meropenem. Isolation of resistant mutants supports that HC2210 requires cofactor F420, although an F420-dependent activating nitroreductase could not be identified. Additionally, resistance mutations in glycerol kinase (glpK) were selected for with HC2210. Transcriptional profiling shows that HC2210 modulates the expression of Mab genes associated with oxidative stress and lipid metabolism, a response that is distinct from Mtb. These findings demonstrate the potential for developing the HC2210 series as a new drug to treat Mab infections.

Systemic Infection Caused by Mycobacterium fortuitum Following Aortic Valve Transplantation—Employing Combined Molecular Techniques for Accurate Species Identification

2025-06-14

Max Roberto Batista Araújo , D Santos , Jailan da Silva Sousa +7 more | Current Microbiology

Digital PCR detection of Mycobacterium tuberculosis and HIV-1 co-localization in spinal tuberculosis biopsies

2025-06-13

Robyn Waters , Adrian R. Martineau , Maritz Laubscher +4 more | bioRxiv (Cold Spring Harbor Laboratory)

ABSTRACT Background. The paucibacillary nature of spinal tuberculosis (STB) makes diagnosis challenging, particularly in people living with HIV-1 (PLWH). It is suggested that HIV-1 and Mycobacterium tuberculosis ( Mtb ) … ABSTRACT Background. The paucibacillary nature of spinal tuberculosis (STB) makes diagnosis challenging, particularly in people living with HIV-1 (PLWH). It is suggested that HIV-1 and Mycobacterium tuberculosis ( Mtb ) co-infection in tissues favours reciprocal replication, infection and reservoir expansion. Yet, confirmation of this detrimental synergism in diseased tissues is scant. Methods In a prospective study of 25 adults (13 (52%) people living with HIV-1 (PLWH) on antiretroviral treatment (ART)) undergoing spinal biopsy investigation for STB in South Africa, droplet digital PCR (ddPCR) was used to detect and quantify Mtb complex (MTBC) DNA ( rpoB and IS6110 ) in 93 biopsy segments, and HIV-1 DNA ( pol and gag ) in 41 segments from PLWH. ddPCR sensitivity for Mtb was validated against Xpert-Ultra and culture. Relationships between pathogen DNA abundance, co-detection, human cellularity, HIV status, and peripheral viral load (VL) were evaluated. Findings ddPCR detected MTBC DNA in 19/25 (76%) patients (range: 8- 59,144 rpoB copies/biopsy), with increased detection in those with confirmed STB and a history of TB. MTBC rpoB copies/million cells were higher in biopsies from PLWH (p=0.0096) and positively correlated with matched biopsy segment HIV-1 pol copies/million cells (r=0.40; p=0.0003), but not peripheral VL. HIV-1 DNA was detected in all biopsies from PLWH, four with undetectable VL. HIV-1 pol copies/million cells were higher in biopsy segments with MTBC DNA co-detected (p=0.011) and strongly correlated with VL (r=0.91; p=0.0003). Interpretation ddPCR has high sensitivity for Mtb and HIV-1 DNA quantification in STB biopsies. Mtb tissue abundance correlated with localised but not systemic HIV-1 abundance. Increased HIV-1 DNA detection at sites co-localised with Mtb supports further investigating the TB microenvironment as a site for HIV-1 reservoir persistence and expansion in PLWH on ART. Funding Wellcome (203135Z/16/Z); Academy of Science of SA (ASSAf); ORU, UCT; UCT Merit Award. Contacts Anna Coussens, Walter and Eliza Hall Institute of Medical Research (WEHI), 1G Royal Parade, Parkville, 3052, Australia; Tel: +61 3 39452699; Email: [email protected] Robyn Waters, Division of Orthopaedic Surgery, University of Cape Town, Anzio Rd, Observatory, 7925, South Africa; Email: [email protected]

Attenuation of a local Mycobacterium avium subsp paratuberculosis virulent strain by homologous recombination

2025-06-01

María Alejandra Colombatti Olivieri , Roberto Damián Moyano , Ariel Nagel +5 more | Research in Veterinary Science