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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 -
Archivos de Bronconeumologia Mar 2021
Topics: Humans; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria
PubMed: 32291100
DOI: 10.1016/j.arbres.2020.02.012 -
PloS One 2023The role of bacterial microbiota in the pathogenesis of nontuberculous mycobacterial pulmonary disease (NTM-PD) is unclear. We aimed to compare the bacterial microbiome...
BACKGROUND
The role of bacterial microbiota in the pathogenesis of nontuberculous mycobacterial pulmonary disease (NTM-PD) is unclear. We aimed to compare the bacterial microbiome of disease-invaded lesions and non-invaded lung tissue from NTM-PD patients.
METHODS
We analyzed lung tissues from 23 NTM-PD patients who underwent surgical lung resection. Lung tissues were collected in pairs from each patient, with one sample from a disease-involved site and the other from a non-involved site. Lung tissue microbiome libraries were constructed using 16S rRNA gene sequences (V3-V4 regions).
RESULTS
Sixteen (70%) patients had Mycobacterium avium complex (MAC)-PD, and the remaining seven (30%) had Mycobacterium abscessus-PD. Compared to non-involved sites, involved sites showed greater species richness (ACE, Chao1, and Jackknife analyses, all p = 0.001); greater diversity on the Shannon index (p = 0.007); and genus-level differences (Jensen-Shannon, PERMANOVA p = 0.001). Analysis of taxonomic biomarkers using linear discriminant analysis (LDA) effect sizes (LEfSe) demonstrated that several genera, including Limnohabitans, Rahnella, Lachnospira, Flavobacterium, Megamonas, Gaiella, Subdoligranulum, Rheinheimera, Dorea, Collinsella, and Phascolarctobacterium, had significantly greater abundance in involved sites (LDA >3.00, p <0.05, and q <0.05). In contrast, Acinetobacter had significantly greater abundance at non-involved sites (LDA = 4.27, p<0.001, and q = 0.002). Several genera were differentially distributed between lung tissues from MAC-PD (n = 16) and M. abscessus-PD (n = 7), and between nodular bronchiectatic form (n = 12) and fibrocavitary form (n = 11) patients. However, there was no genus with a significant q-value.
CONCLUSIONS
We identified differential microbial distributions between disease-invaded and normal lung tissues from NTM-PD patients, and microbial diversity was significantly higher in disease-invaded tissues.
TRIAL REGISTRATION
Clinical Trial registration number: NCT00970801.
Topics: Humans; RNA, Ribosomal, 16S; Mycobacterium Infections, Nontuberculous; Mycobacterium avium Complex; Lung Diseases; Lung; Microbiota; Nontuberculous Mycobacteria
PubMed: 37235629
DOI: 10.1371/journal.pone.0285143 -
Critical Reviews in Microbiology Aug 2023is a nontuberculous mycobacterium, associated with broncho-pulmonary infections in individuals suffering from cystic fibrosis, bronchiectasis, and pulmonary diseases.... (Review)
Review
is a nontuberculous mycobacterium, associated with broncho-pulmonary infections in individuals suffering from cystic fibrosis, bronchiectasis, and pulmonary diseases. The risk factors for transmission include biofilms, contaminated water resources, fomites, and infected individuals. is extensively resistant to antibiotics. To date, there is no vaccine and combination antibiotic therapy is followed. However, drug toxicities, low cure rates, and high cost of treatment make it imperfect. Over the last 20 years, bioinformatic studies on have advanced our understanding of the pathogen. This review integrates knowledge from the analysis of genomes, microbiomes, genomic variations, phylogeny, proteome, transcriptome, secretome, antibiotic resistance, and vaccine design to further our understanding. The utility of genome-based studies in comprehending disease progression, surveillance, tracing transmission routes, and epidemiological outbreaks on a global scale has been highlighted. Furthermore, this review underlined the importance of using computational methodologies for pinpointing factors responsible for pathogen survival and resistance. We reiterate the significance of interdisciplinary research to fight In a nutshell, the outcome of computational studies can go a long way in creating novel therapeutic avenues to control mediated pulmonary infections.
Topics: Humans; Mycobacterium abscessus; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Cystic Fibrosis; Anti-Bacterial Agents
PubMed: 35696783
DOI: 10.1080/1040841X.2022.2082268 -
Chest Jan 2022
Topics: Cystic Fibrosis; Humans; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Thorax
PubMed: 35000697
DOI: 10.1016/j.chest.2021.06.054 -
Mayo Clinic Proceedings Aug 2019Nontuberculous mycobacteria (NTM) comprise a heterogeneous group of organisms, with only a small subset known to cause disease in humans. Although NTM infection is not a... (Review)
Review
Nontuberculous mycobacteria (NTM) comprise a heterogeneous group of organisms, with only a small subset known to cause disease in humans. Although NTM infection is not a reportable disease, both the increasing clinical recognition and recent advancements in laboratory diagnostic capabilities of NTM infections in immunocompromised and immunocompetent patients are rapidly evolving. We reviewed antimicrobial agents used to treat the most frequently encountered NTM infections and examined optimized drug dosing strategies, toxicity profiles, drug-drug interactions, and the role of therapeutic drug monitoring. Antimicrobial susceptibility testing and patient monitoring on therapy were also examined. We used PubMed to review the published literature on the management of select NTM pathogens, the common syndromes encountered since 2000, and select pharmacokinetic principles of select antimicrobial agents used since 1990. We included select clinical trials, systematic reviews, published guidelines, and observational studies when applicable. The prolonged duration and the necessity for combination therapy for most forms of NTM disease can be problematic for many patients. A multidisciplinary care team that includes pharmacy engagement may help increase rates of optimal patient tolerability and successful treatment completion.
Topics: Anti-Bacterial Agents; Drug Monitoring; Female; Follow-Up Studies; Humans; Immunocompetence; Immunocompromised Host; Incidence; Interdisciplinary Communication; Male; Maximum Tolerated Dose; Microbial Sensitivity Tests; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Patient Safety; Risk Assessment
PubMed: 31160063
DOI: 10.1016/j.mayocp.2018.12.011 -
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 -
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