Defects in DNA double-strand break repair resensitize antibiotic-resistant Escherichia coli to multiple bactericidal antibiotics.

ABSTRACT: Antibiotic resistance is becoming increasingly prevalent amongst bacterial pathogens and there is an urgent need to develop new types of antibiotics with novel modes of action. One promising strategy is to develop resistance-breaker compounds, which inhibit resistance mechanisms and thus resensitize bacteria to existing antibiotics. In the current study, we identify bacterial DNA double-strand break repair as a promising target for the development of resistance-breaking co-therapies. We examined genetic variants of Escherichia coli that combined antibiotic-resistance determinants with DNA repair defects. We observed that defects in the double-strand break repair pathway led to significant resensitization toward five bactericidal antibiotics representing different functional classes. Effect

SUBMITTER: Revitt-Mills SA 

PROVIDER: S-EPMC9500592 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature