Rapid evolution of colistin resistance in a bioreactor model of infection of Klebsiella pneumoniae.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
01 Jul 2024
01 Jul 2024
Historique:
received:
16
03
2023
accepted:
23
05
2024
medline:
2
7
2024
pubmed:
2
7
2024
entrez:
1
7
2024
Statut:
epublish
Résumé
Colistin remains an important antibiotic for the therapeutic management of drug-resistant Klebsiella pneumoniae. Despite the numerous reports of colistin resistance in clinical strains, it remains unclear exactly when and how different mutational events arise resulting in reduced colistin susceptibility. Using a bioreactor model of infection, we modelled the emergence of colistin resistance in a susceptible isolate of K. pneumoniae. Genotypic, phenotypic and mathematical analyses of the antibiotic-challenged and un-challenged population indicates that after an initial decline, the population recovers within 24 h due to a small number of "founder cells" which have single point mutations mainly in the regulatory genes encoding crrB and pmrB that when mutated results in up to 100-fold reduction in colistin susceptibility. Our work underlines the rapid development of colistin resistance during treatment or exposure of susceptible K. pneumoniae infections having implications for the use of cationic antimicrobial peptides as a monotherapy.
Identifiants
pubmed: 38951173
doi: 10.1038/s42003-024-06378-0
pii: 10.1038/s42003-024-06378-0
doi:
Substances chimiques
Colistin
Z67X93HJG1
Anti-Bacterial Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
794Subventions
Organisme : RCUK | Medical Research Council (MRC)
ID : MR/P007597/1
Informations de copyright
© 2024. The Author(s).
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