Dynamics of Extensive Drug Resistance Evolution of Mycobacterium tuberculosis in a Single Patient During 9 Years of Disease and Treatment.
Mycobacterium tuberculosis
antibiotic resistance
evolution
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
15 03 2022
15 03 2022
Historique:
received:
26
06
2020
accepted:
08
10
2020
pubmed:
13
10
2020
medline:
10
5
2022
entrez:
12
10
2020
Statut:
ppublish
Résumé
Mycobacterium tuberculosis is one of the hardest to treat bacterial pathogens with a high capacity to develop antibiotic resistance by mutations. Here we have performed whole-genome sequencing of consecutive M. tuberculosis isolates obtained during 9 years from a patient with pulmonary tuberculosis. The infecting strain was isoniazid resistant and during treatment it stepwise accumulated resistance mutations to 8 additional antibiotics. Heteroresistance was common and subpopulations with up to 3 different resistance mutations to the same drug coexisted. Sweeps of different resistant clones dominated the population at different time points, always coupled to resistance mutations coinciding with changes in the treatment regimens. Resistance mutations were predominant and no hitch-hiking, compensatory, or virulence-increasing mutations were detected, showing that the dominant selection pressure was antibiotic treatment. The results highlight the dynamic nature of M. tuberculosis infection, population structure, and resistance evolution and the importance of rapid antibiotic susceptibility tests to battle this pathogen.
Identifiants
pubmed: 33045067
pii: 5921146
doi: 10.1093/infdis/jiaa625
pmc: PMC8921999
doi:
Substances chimiques
Antitubercular Agents
0
Isoniazid
V83O1VOZ8L
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1011-1020Informations de copyright
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.
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