Whole-Cell Assays for Discovering Novel Efflux Inhibitors for Use as Antibiotic Adjuvants

Abstract

Antimicrobial resistance (AMR) is a growing problem worldwide. Resistance to antibiotics can occur in a number of ways, one of which is removal of the drugs from the cell via efflux pump macromolecular machineries. As such, efflux pumps can provide a background level of resistance to many different classes of antimicrobials and are a major contributor to AMR. Inhibition of efflux pumps therefore has the potential to reverse resistance to many antibiotics in one go and is an attractive potential for treating resistant infections. Whilst a number of efflux inhibitors are known, none are currently used clinically due to harmful side effects. Development of novel inhibitors is therefore imperative. The article aims to review accumulation assays and efflux assays, two of the most common laboratory techniques used to identify and characterise candidate efflux inhibitors.