Cryptic β-Lactamase Evolution Is Driven by Low β-Lactam Concentrations.

ABSTRACT: Our current understanding of how low antibiotic concentrations shape the evolution of contemporary β-lactamases is limited. Using the widespread carbapenemase OXA-48, we tested the long-standing hypothesis that selective compartments with low antibiotic concentrations cause standing genetic diversity that could act as a gateway to developing clinical resistance. Here, we subjected Escherichia coli expressing bla_OXA-48, on a clinical plasmid, to experimental evolution at sub-MICs of ceftazidime. We identified and characterized seven single variants of OXA-48. Susceptibility profiles and dose-response curves showed that they increased resistance only marginally. However, in competition experiments at sub-MICs of ceftazidime, they demonstrated strong selectable fitnes

SUBMITTER: Frohlich C 

PROVIDER: S-EPMC8092134 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature