Rapid Evolution of Colistin Resistance in a Bioreactor Model of Infection of Klebsiella pneumoniae

Juan-Carlos Jiménez-Castellanos, B. Waclaw, Alison M Meynert, Sean McAteer, Thamarai Schneiders

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Colis1n remains an important an1bio1c for the therapeu1c management of drug-resistant Klebsiella pneumoniae. Despite the numerous reports of colis1n resistance in clinical strains, it remains unclear exactly when and how different muta1onal events arise resul1ng in reduced colis1n suscep1bility. Using a bioreactor model of infec1on, we modelled the emergence of colis1n resistance in a suscep1ble isolate of K. pneumoniae. Genotypic, phenotypic and mathema1cal analyses of the an1bio1c challenged and un-challenged popula1on indicates that aKer an ini1al decline, the popula1on recovers within 24h due to a small number of “founder cells” which have single point muta1ons mainly in the regulatory genes encoding crrB and pmrB that when mutated results in up to 100-fold reduc1on in colis1n suscep1bility. Our work underlines the rapid development of colis1n resistance during treatment or exposure of suscep1ble K. pneumoniae infec1ons having implica1ons for the use of ca1onic an1microbial pep1des as a monotherapy.
Original languageEnglish
JournalCommunications Biology
DOIs
Publication statusPublished - 1 Jul 2024

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