Analysis of Orthogonal Efflux and Permeation Properties of Compounds Leads to the Discovery of New Efflux Pump Inhibitors.

ABSTRACT: Optimization of compound permeation into Gram-negative bacteria is one of the most challenging tasks in the development of antibacterial agents. Two permeability barriers─the passive diffusion barrier of the outer membrane (OM) and active drug efflux─act synergistically to protect cells from the antibacterial action of compounds. In Escherichia coli (E. coli) and relatives, these two barriers sieve compounds based on different physicochemical properties that are defined by their interactions with OM porins and efflux pumps, respectively. In this study, we critically tested the hypothesis that the best substrates and inhibitors of efflux pumps are compounds that can effectively permeate the OM and are available at relatively high concentrations in the periplasm. For this purpo

SUBMITTER: Moniruzzaman M 

PROVIDER: S-EPMC9942517 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature