Clinically relevant mutations in core metabolic genes confer antibiotic resistance.

ABSTRACT: Although metabolism plays an active role in antibiotic lethality, antibiotic resistance is generally associated with drug target modification, enzymatic inactivation, and/or transport rather than metabolic processes. Evolution experiments of Escherichia coli rely on growth-dependent selection, which may provide a limited view of the antibiotic resistance landscape. We sequenced and analyzed E. coli adapted to representative antibiotics at increasingly heightened metabolic states. This revealed various underappreciated noncanonical genes, such as those related to central carbon and energy metabolism, which are implicated in antibiotic resistance. These metabolic alterations lead to lower basal respiration, which prevents antibiotic-mediated induction of tricarboxylic acid cycl

SUBMITTER: Lopatkin AJ 

PROVIDER: S-EPMC8285040 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature