Comparative reassessment of AcrB efflux inhibitors reveals differential impact of specific pump mutations on the activity of potent compounds.

ABSTRACT: Multidrug resistance poses global challenges, particularly with regard to Gram-negative bacterial infections. In view of the lack of new antibiotics, drug enhancers, such as efflux pump inhibitors (EPIs), have increasingly come into focus. A number of chemically diverse agents have been reported to inhibit AcrB, the main multidrug transporter in Escherichia coli, and homologs in other Gram-negative bacteria. However, due to the often varying methodologies used for their characterization, results remain difficult to compare. In this study, using a defined selection of antibiotics known to be efflux substrates, we reevaluated 38 published compounds for their in vitro EPI activity. When examined in an E. coli strain with stable wild-type AcrB overexpression, we found 17 c

SUBMITTER: Schuster S 

PROVIDER: S-EPMC10846202 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature