Rapid evolution of colistin resistance in a bioreactor model of infection of Klebsiella pneumoniae.

Autor: Jiménez-Castellanos JC; Chemical Biology of Antibiotics, Centre for Infection & Immunity (CIIL), Pasteur Institute, INSERM U1019-CNRS UMR 9017, Lille, France., Waclaw B; School of Physics and Astronomy, The University of Edinburgh, JCMB, Edinburgh, UK. bwaclaw@ed.ac.uk.; Dioscuri Centre for Physics and Chemistry of Bacteria, Institute of Physical Chemistry, Warsaw, Poland. bwaclaw@ed.ac.uk., Meynert A; MRC Human Genetics Unit, MRC Institute of Genetics and Cancer, The University of Edinburgh, Western General Hospital, Edinburgh, UK., McAteer SP; Department of Bacteriology, The Roslin Institute and R(D) SVS, The University of Edinburgh, Easter Bush Campus, Midlothian, Edinburgh, UK., Schneiders T; Centre for Inflammation Research, Institute of Regeneration and Repair, Edinburgh Medical School, The University of Edinburgh, Edinburgh, UK. Thamarai.Schneiders@ed.ac.uk.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2024 Jul 01; Vol. 7 (1), pp. 794. Date of Electronic Publication: 2024 Jul 01.
DOI: 10.1038/s42003-024-06378-0
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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