Targeting MarA N-terminal domain dynamics to prevent DNA binding.

ABSTRACT: Efflux is one of the mechanisms employed by Gram-negative bacteria to become resistant to routinely used antibiotics. The inhibition of efflux by targeting their regulators is a promising strategy to re-sensitize bacterial pathogens to antibiotics. AcrAB-TolC is the main resistance-nodulation-division efflux pump in Enterobacteriaceae. MarA is an AraC/XylS family global regulator that regulates more than 40 genes related to the antimicrobial resistance phenotype, including acrAB. The aim of this work was to understand the role of the N-terminal helix of MarA in the mechanism of DNA binding. An N-terminal deletion of MarA showed that the N-terminal helix is critical for recognition of the functional marboxes. By engineering two double cysteine variants of MarA that form a disulfide bond bet

SUBMITTER: Corbella M 

PROVIDER: S-EPMC11633057 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature