A small-molecule inhibitor of BamA impervious to efflux and the outer membrane permeability barrier.

ABSTRACT: The development of new antimicrobial drugs is a priority to combat the increasing spread of multidrug-resistant bacteria. This development is especially problematic in gram-negative bacteria due to the outer membrane (OM) permeability barrier and multidrug efflux pumps. Therefore, we screened for compounds that target essential, nonredundant, surface-exposed processes in gram-negative bacteria. We identified a compound, MRL-494, that inhibits assembly of OM proteins (OMPs) by the β-barrel assembly machine (BAM complex). The BAM complex contains one essential surface-exposed protein, BamA. We constructed a bamA mutagenesis library, screened for resistance to MRL-494, and identified the mutation bamA _E470K BamA^E470K restores OMP biogenesis in the pr

SUBMITTER: Hart EM 

PROVIDER: S-EPMC6815139 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature