Copy number flexibility facilitates heteroresistance to increasing antibiotic pressure and threatens the beta-lactam pipeline.

ABSTRACT: Our understanding of the rapid adaptation of bacteria to resist novel drugs is growing beyond known mechanisms such as mobile genetic elements and mutation selection. Heteroresistance (HR) is a form of antibiotic resistance where a phenotypically unstable minority resistant subpopulation co-exists with a susceptible population. We sought to uncover the mechanism of heteroresistance to cefiderocol, a novel β-lactam developed to resist β-lactamases including extended-spectrum-β-lactamases (ESBLs), which has been recently reported but poorly understood. We observe HR to cefiderocol among clinical isolates collected before its use. The resistant subpopulation in Enterobacter is a continuum; increasing copy number of a gene encoding an ESBL ineffective against cefiderocol mediates increased res

SUBMITTER: Choby JE 

PROVIDER: S-EPMC12216759 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature