Counteracting antibiotic resistance enzymes and efflux pumps

Abstract

Bacterial pathogens are constantly evolving new resistance mechanisms against antibiotics; hence, strategies to potentiate existing antibiotics or combat mechanisms of resistance using adjuvants are always in demand. Recently, inhibitors have been identified that counteract enzymatic modification of the drugs isoniazid and rifampin, which have implications in the study of multi-drug-resistant mycobacteria. A wealth of structural studies on efflux pumps from diverse bacteria has also fueled the design of new small-molecule and peptide-based agents to prevent the active transport of antibiotics. We envision that these findings will inspire microbiologists to apply existing adjuvants to clinically relevant resistant strains, or to use described platforms to discover novel antibiotic adjuvant scaffolds.