Impeding pathways of intrinsic resistance in Escherichia coli confers antibiotic sensitization and resistance proofing.

ABSTRACT: Pathways of intrinsic resistance in bacteria are promising targets for novel antibiotics and resistance breakers. Here, we used a genome-wide screen to identify single gene knockouts of Escherichia coli that were hypersusceptible to trimethoprim and chloramphenicol, two chemically diverse broad-spectrum antibiotics. Among the hits from our screen, knockouts of acrB, an efflux pump, and rfaG or lpxM, both involved in cell envelope biogenesis, were hypersensitive to multiple antimicrobials and could sensitize genetically resistant E. coli strains to antibiotics. Using experimental evolution under trimethoprim pressure, we show that high drug selection regimes drove these knockouts to extinction more frequently than wild type. Among them, ΔacrB was most compromised in its ability to evolve re

SUBMITTER: Balachandran M 

PROVIDER: S-EPMC12543169 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature