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Clinics in Chest Medicine Mar 2015Population-based data have documented a worldwide increase in the prevalence of human nontuberculous mycobacterial (NTM) infections since 2000. Mycobacterium avium... (Review)
Review
Population-based data have documented a worldwide increase in the prevalence of human nontuberculous mycobacterial (NTM) infections since 2000. Mycobacterium avium complex is predominant in North America and East Asia, whereas in regions within Europe, M kansasii, M xenopi, and M malmoense are more common. Host factors important to the current epidemiology of NTM pulmonary disease include thoracic skeletal abnormalities, rheumatoid arthritis, and use of immunomodulatory drugs. Clustering of disease within families suggests a heritable genetic predisposition to disease susceptibility. Warm, humid environments with high atmospheric vapor pressure contribute to population risk.
Topics: Global Health; Humans; Lung Diseases; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Prevalence
PubMed: 25676516
DOI: 10.1016/j.ccm.2014.10.002 -
Frontiers in Immunology 2022Non-tuberculous mycobacteria (NTM) are a heterogeneous group of originally environmental organi3sms, increasingly recognized as pathogens with rising prevalence... (Review)
Review
Non-tuberculous mycobacteria (NTM) are a heterogeneous group of originally environmental organi3sms, increasingly recognized as pathogens with rising prevalence worldwide. Knowledge of NTM's mechanisms of virulence is lacking, as molecular research of these bacteria is challenging, sometimes more than that of M. tuberculosis (Mtb), and far less resources are allocated to their investigation. While some of the virulence mechanisms are common to several mycobacteria including Mtb, others NTM species-specific. Among NTMs, Mycobacterium abscessus (Mabs) causes some of the most severe and difficult to treat infections, especially chronic pulmonary infections. Mabs survives and proliferates intracellularly by circumventing host defenses, using multiple mechanisms, many of which remain poorly characterized. Some of these immune-evasion mechanisms are also found in Mtb, including phagosome pore formation, inhibition of phagosome maturation, cytokine response interference and apoptosis delay. While much is known of the role of Mtb-secreted effector molecules in mediating the manipulation of the host response, far less is known of the secreted effector molecules in Mabs. In this review, we briefly summarize the knowledge of secreted effectors in Mtb (such as ESX secretion, SecA2, TAT and others), and draw the parallel pathways in Mabs. We also describe pathways that are unique to Mabs, differentiating it from Mtb. This review will assist researchers interested in virulence-associated secretion in Mabs by providing the knowledge base and framework for their studies.
Topics: Mycobacterium abscessus; Mycobacterium tuberculosis; Nontuberculous Mycobacteria; Phagosomes; Virulence
PubMed: 35880173
DOI: 10.3389/fimmu.2022.938895 -
Immunological Reviews May 2021Upon infection, mycobacteria, such as Mycobacterium tuberculosis (Mtb) and nontuberculous mycobacteria (NTM), are recognized by host innate immune cells, triggering a... (Review)
Review
Upon infection, mycobacteria, such as Mycobacterium tuberculosis (Mtb) and nontuberculous mycobacteria (NTM), are recognized by host innate immune cells, triggering a series of intracellular processes that promote mycobacterial killing. Mycobacteria, however, have developed multiple counter-strategies to persist and survive inside host cells. By manipulating host effector mechanisms, including phagosome maturation, vacuolar escape, autophagy, antigen presentation, and metabolic pathways, pathogenic mycobacteria are able to establish long-lasting infection. Counteracting these mycobacteria-induced host modifying mechanisms can be accomplished by host-directed therapeutic (HDT) strategies. HDTs offer several major advantages compared to conventional antibiotics: (a) HDTs can be effective against both drug-resistant and drug-susceptible bacteria, as well as potentially dormant mycobacteria; (b) HDTs are less likely to induce bacterial drug resistance; and (c) HDTs could synergize with, or shorten antibiotic treatment by targeting different pathways. In this review, we will explore host-pathogen interactions that have been identified for Mtb for which potential HDTs impacting both innate and adaptive immunity are available, and outline those worthy of future research. We will also discuss possibilities to target NTM infection by HDT, although current knowledge regarding host-pathogen interactions for NTM is limited compared to Mtb. Finally, we speculate that combinatorial HDT strategies can potentially synergize to achieve optimal mycobacterial host immune control.
Topics: Anti-Bacterial Agents; Autophagy; Host-Pathogen Interactions; Mycobacterium tuberculosis; Nontuberculous Mycobacteria
PubMed: 33565103
DOI: 10.1111/imr.12951 -
Ethiopian Journal of Health Sciences Sep 2023Non-tuberculous mycobacteria (NTM) have been reported to cause pulmonary and extrapulmonary infections. These NTMs are often misdiagnosed as MTB due to their similar... (Review)
Review
BACKGROUND
Non-tuberculous mycobacteria (NTM) have been reported to cause pulmonary and extrapulmonary infections. These NTMs are often misdiagnosed as MTB due to their similar clinical presentations to tuberculosis, leading to inappropriate treatment and increased morbidity and mortality rates. This literature review aims to provide an overview of the prevalence, clinical manifestations, diagnosis, and management of NTM infections in Africa.
METHODS
A systematic search was performed using various electronic databases including PubMed, Scopus, and Web of Science. The search was limited to studies published in the English language from 2000 to 2021. The following keywords were used: "non-tuberculous mycobacteria", "NTM", "Africa", and "prevalence". Studies that focused solely on the Mycobacterium tuberculosis complex or those that did not report prevalence rates were excluded. Data extraction was performed on eligible studies. Overall, a total of 32 studies met the inclusion criteria and were included in this review.
RESULTS
In our literature review, we identified a total of 32 studies that reported non-tuberculosis mycobacteria (NTM) in Africa. The majority of these studies were conducted in South Africa, followed by Ethiopia and Nigeria. The most commonly isolated NTM species were Mycobacterium avium complex (MAC), Mycobacterium fortuitum, and Mycobacterium abscessus. Many of the studies reported a high prevalence of NTM infections among HIV-positive individuals. Other risk factors for NTM infection included advanced age, chronic lung disease, and previous tuberculosis infection.
CONCLUSION
In conclusion, this literature review highlights the significant burden of non-tuberculosis mycobacteria infections in Africa. The prevalence of these infections is high, and they are often misdiagnosed due to their similarity to tuberculosis. The lack of awareness and diagnostic tools for non-tuberculosis mycobacteria infections in Africa is a major concern that needs to be addressed urgently. It is crucial to improve laboratory capacity and develop appropriate diagnostic algorithms for these infections.
Topics: Humans; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Africa; Prevalence
PubMed: 38784502
DOI: 10.4314/ejhs.v33i5.21 -
F1000Research 2019Nontuberculous mycobacteria (NTM) are members of the Mycobacterium genus other than complex and . NTM are widely distributed in the environment and are increasingly... (Review)
Review
Nontuberculous mycobacteria (NTM) are members of the Mycobacterium genus other than complex and . NTM are widely distributed in the environment and are increasingly recognized as causes of chronic lung disease that can be challenging to treat. In this brief review, we consider recent developments in the ecology, epidemiology, natural history, and treatment of NTM lung disease with a focus on complex (MAC) and complex
Topics: Humans; Lung Diseases; Mycobacterium Infections, Nontuberculous; Mycobacterium abscessus; Mycobacterium avium Complex
PubMed: 31602293
DOI: 10.12688/f1000research.20096.1 -
International Journal of Molecular... Jul 2023, a species of nontuberculous mycobacteria (NTM), is an opportunistic pathogen that is readily cleared by healthy lungs but can cause pulmonary infections in people with...
, a species of nontuberculous mycobacteria (NTM), is an opportunistic pathogen that is readily cleared by healthy lungs but can cause pulmonary infections in people with chronic airway diseases. Although knowledge pertaining to molecular mechanisms of host defense against NTM is increasing, macrophage receptors that recognize remain poorly defined. Dectin-1, a C-type lectin receptor identified as a fungal receptor, has been shown to be a pathogen recognition receptor (PRR) for both and NTM. To better understand the role of Dectin-1 in host defense against , we tested whether blocking Dectin-1 impaired the uptake of by human macrophages, and we compared pulmonary infection in Dectin-1-deficient and wild-type mice. Blocking antibody for Dectin-1 did not reduce macrophage phagocytosis of , but did reduce the ingestion of the fungal antigen zymosan. Laminarin, a glucan that blocks Dectin-1 and other PRRs, caused decreased phagocytosis of both and zymosan. Dectin-1-/- mice exhibited no defects in the control of infection, and no differences were detected in immune cell populations between wild type and Dectin-1-/- mice. These data demonstrate that murine defense against pulmonary infection, as well as ingestion of by human macrophages, can occur independent of Dectin-1. Thus, additional PRR(s) recognized by laminarin participate in macrophage phagocytosis of
Topics: Humans; Animals; Mice; Mycobacterium abscessus; Zymosan; Macrophages; Phagocytosis; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous
PubMed: 37446240
DOI: 10.3390/ijms241311062 -
Journal of Clinical Microbiology Oct 2019Recommendations for first-line and second-line drug testing and organism group, specific methodologies, and reporting recommendations have been addressed by the Clinical... (Review)
Review
Recommendations for first-line and second-line drug testing and organism group, specific methodologies, and reporting recommendations have been addressed by the Clinical and Laboratory Standards Institute (CLSI) and are important in the selection of appropriate antimicrobial treatment regimens for nontuberculous mycobacteria (NTM) disease. This review also includes recent information on new antimicrobials proposed for the treatment of NTM but not yet addressed by the CLSI and molecular (gene sequencing) methods associated with the detection of antimicrobial resistance of two major therapeutic antimicrobials, clarithromycin and amikacin.
Topics: Anti-Bacterial Agents; Bacteriological Techniques; Humans; Microbial Sensitivity Tests; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria
PubMed: 31315954
DOI: 10.1128/JCM.00834-19 -
Emerging Infectious Diseases Aug 2023Nontuberculous mycobacteria (NTM) infections are caused by environmental exposure. We describe spatial distribution of NTM infections and associations with... (Review)
Review
Nontuberculous mycobacteria (NTM) infections are caused by environmental exposure. We describe spatial distribution of NTM infections and associations with sociodemographic factors and flooding in Missouri, USA. Our retrospective analysis of mycobacterial cultures reported to the Missouri Department of Health and Social Services surveillance system during January 1, 2008-December 31, 2019, detected geographic clusters of infection. Multilevel Poisson regression quantified small-area geographic variations and identified characteristics associated with risk for infection. Median county-level NTM infection rate was 66.33 (interquartile range 51-91)/100,000 persons. Risk of clustering was significantly higher in rural areas (rate ratio 2.82, 95% CI 1.90-4.19) and in counties with >5 floodings per year versus no flooding (rate ratio 1.38, 95% CI 1.26-1.52). Higher risk for NTM infection was associated with older age, rurality, and more flooding. Clinicians and public health professionals should be aware of increased risk for NTM infections, especially in similar environments.
Topics: Humans; Missouri; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Prevalence; Retrospective Studies; Risk Factors; Age Factors; Floods; Rural Population; Male; Female; Middle Aged; Aged; Disease Hotspot
PubMed: 37486160
DOI: 10.3201/eid2908.230378 -
Antimicrobial Agents and Chemotherapy Jun 2023Benzoxaboroles are a new class of leucyl-tRNA synthetase inhibitors. Epetraborole, a benzoxaborole, is a clinical candidate developed for Gram-negative infections and...
Benzoxaboroles are a new class of leucyl-tRNA synthetase inhibitors. Epetraborole, a benzoxaborole, is a clinical candidate developed for Gram-negative infections and has been confirmed to exhibit favorable activity against a well known pulmonary pathogen, Mycobacterium abscessus. However, according to ClinicalTrials.gov, in 2017, a clinical phase II study on the use of epetraborole to treat complicated urinary tract and intra-abdominal infections was terminated due to the rapid emergence of drug resistance during treatment. Nevertheless, epetraborole is in clinical development for nontuberculous mycobacteria (NTM) disease especially for Mycobacterium avium complex-related pulmonary disease (MAC-PD). DS86760016, an epetraborole analog, was further demonstrated to have an improved pharmacokinetic profile, lower plasma clearance, longer plasma half-life, and higher renal excretion than epetraborole in animal models. In this study, DS86760016 was found to be similarly active against M. abscessus , intracellularly, and in zebrafish infection models with a low mutation frequency. These results expand the diversity of druggable compounds as new benzoxaborole-based candidates for treating M. abscessus diseases.
Topics: Animals; Mycobacterium abscessus; Zebrafish; Mycobacterium Infections, Nontuberculous; Anti-Bacterial Agents; Amino Acyl-tRNA Synthetases; Nontuberculous Mycobacteria
PubMed: 37212672
DOI: 10.1128/aac.01567-22 -
Frontiers in Cellular and Infection... 2023We aimed to evaluate the activity of PBTZ169 and pretomanid against non-tuberculous mycobacteriosis (NTM) and .
OBJECTIVES
We aimed to evaluate the activity of PBTZ169 and pretomanid against non-tuberculous mycobacteriosis (NTM) and .
METHODS
The minimum inhibitory concentrations (MICs) of 11 antibiotics, against slow-growing mycobacteria (SGMs) and rapid-growing mycobacteria (RGMs) were tested using the microplate alamarBlue assay. The activities of bedaquiline, clofazimine, moxifloxacin, rifabutin, PBTZ169 and pretomanid against four common NTMs were assessed in murine models.
RESULTS
PBTZ169 and pretomanid had MICs of >32 μg/mL against most NTM reference and clinical strains. However, PBTZ169 was bactericidal against (3.33 and 1.49 log10 CFU reductions in the lungs and spleen, respectively) and (2.29 and 2.24 CFU reductions in the lungs and spleen, respectively) in mice, and bacteriostatic against Mycobacterium avium and . Pretomanid dramatically decreased the CFU counts of (3.12 and 2.30 log10 CFU reductions in the lungs and spleen, respectively), whereas it showed moderate inhibition of and . Bedaquiline, clofazimine, and moxifloxacin showed good activities against four NTMs and . Rifabutin did not inhibit and in mice.
CONCLUSION
PBTZ169 appears to be a candidate for treating four common NTM infections. Pretomanid was more active against , and than against .
Topics: Animals; Mice; Mycobacterium abscessus; Mycobacterium avium; Mycobacterium fortuitum; Mycobacterium chelonae; Clofazimine; Moxifloxacin; Mice, Inbred BALB C; Anti-Bacterial Agents; Nontuberculous Mycobacteria; Mycobacterium Infections; Rifabutin; Mycobacterium Infections, Nontuberculous; Microbial Sensitivity Tests
PubMed: 37077530
DOI: 10.3389/fcimb.2023.1115530