Bacterial efflux pump modulators prevent bacterial growth in macrophages and under broth conditions that mimic the host environment.

ABSTRACT:

Importance

Bacterial efflux pumps are critical for resistance to antibiotics and for virulence. We previously identified small molecules that inhibit efflux pumps (efflux pump modulators, EPMs) and prevent pathogen replication in host cells. Here, we used medicinal chemistry to increase the activity of the EPMs against pathogens in cells into the nanomolar range. We show by cryo-electron microscopy that these EPMs bind an efflux pump subunit. In broth culture, the EPMs increase the potency (activity), but not the efficacy (maximum effect), of antibiotics. We also found that bacterial exposure to the EPMs appear to enable the accumulation of a toxic metabolite that would otherwise be exported by efflux pumps. Thus, inhibitors of bacterial efflux pumps could interfere with infection

SUBMITTER: Allgood SC 

PROVIDER: S-EPMC10746280 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature