Genetic Determinants of Intrinsic Antibiotic Tolerance in Mycobacterium avium.
Anti-Bacterial Agents
/ pharmacology
Clarithromycin
/ pharmacology
DNA Transposable Elements
/ genetics
Drug Therapy, Combination
Drug Tolerance
/ genetics
Ethambutol
/ pharmacology
Humans
Moxifloxacin
/ pharmacology
Mycobacterium avium Complex
/ drug effects
Mycobacterium avium-intracellulare Infection
/ drug therapy
Rifabutin
/ pharmacology
DNA sequencing
bioinformatics
mechanisms of action
molecular genetics
persistence
tolerance
Journal
Microbiology spectrum
ISSN: 2165-0497
Titre abrégé: Microbiol Spectr
Pays: United States
ID NLM: 101634614
Informations de publication
Date de publication:
31 10 2021
31 10 2021
Historique:
pubmed:
16
9
2021
medline:
2
2
2022
entrez:
15
9
2021
Statut:
ppublish
Résumé
The Mycobacterium avium complex (MAC) is one of the most prevalent causes of nontuberculous mycobacteria pulmonary infection in the United States, and yet it remains understudied. Current MAC treatment requires more than a year of intermittent to daily combination antibiotic therapy, depending on disease severity. In order to shorten and simplify curative regimens, it is important to identify the innate bacterial factors contributing to reduced antibiotic susceptibility, namely, antibiotic tolerance genes. In this study, we performed a genome-wide transposon screen to elucidate M. avium genes that play a role in the bacterium's tolerance to first- and second-line antibiotics. We identified a total of 193 unique M. avium mutants with significantly altered susceptibility to at least one of the four clinically used antibiotics we tested, including two mutants (in DFS55_00905 and DFS55_12730) with panhypersusceptibility. The products of the antibiotic tolerance genes we have identified may represent novel targets for future drug development studies aimed at shortening the duration of therapy for MAC infections.
Identifiants
pubmed: 34523947
doi: 10.1128/Spectrum.00246-21
pmc: PMC8557931
doi:
Substances chimiques
Anti-Bacterial Agents
0
DNA Transposable Elements
0
Rifabutin
1W306TDA6S
Ethambutol
8G167061QZ
Clarithromycin
H1250JIK0A
Moxifloxacin
U188XYD42P
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0024621Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM007057
Pays : United States
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