Emergence of phenotypic and genotypic antimicrobial resistance in Mycobacterium tuberculosis.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
11 Dec 2022
11 Dec 2022
Historique:
received:
01
08
2022
accepted:
05
12
2022
entrez:
12
12
2022
pubmed:
13
12
2022
medline:
15
12
2022
Statut:
epublish
Résumé
Concentration dependency of phenotypic and genotypic isoniazid-rifampicin resistance emergence was investigated to obtain a mechanistic understanding on how anti-mycobacterial drugs facilitate the emergence of bacterial populations that survive throughout treatment. Using static kill curve experiments, observing two evolution cycles, it was demonstrated that rifampicin resistance was the result of non-specific mechanisms and not associated with accumulation of drug resistance encoding SNPs. Whereas, part of isoniazid resistance could be accounted for by accumulation of specific SNPs, which was concentration dependent. Using a Hollow Fibre Infection Model it was demonstrated that emergence of resistance did not occur at concentration-time profiles mimicking the granuloma. This study showed that disentangling and quantifying concentration dependent emergence of resistance provides an improved rational for drug and dose selection although further work to understand the underlying mechanisms is needed to improve the drug development pipeline.
Identifiants
pubmed: 36504241
doi: 10.1038/s41598-022-25827-6
pii: 10.1038/s41598-022-25827-6
pmc: PMC9742156
doi:
Substances chimiques
Anti-Bacterial Agents
0
Isoniazid
V83O1VOZ8L
Rifampin
VJT6J7R4TR
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
21429Subventions
Organisme : Medical Research Council
ID : MR/P014534/1
Pays : United Kingdom
Informations de copyright
© 2022. The Author(s).
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