Structural and functional diversity of Resistance-Nodulation-Division (RND) efflux pump transporters with implications for antimicrobial resistance

• Published in: Microbiology and molecular biology reviews 2024-09, Vol.88 (3), p.e0008923
• Main Authors: Kavanaugh, Logan G, Dey, Debayan, Shafer, William M, Conn, Graeme L
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - pharmacology; Antibiotics; Antimicrobial agents; Antimicrobial resistance; Bacteria; Bacteria - drug effects; Bacteria - metabolism; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biocides; Cytotoxicity; Disease resistance; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Efflux; Gram-negative bacteria; Gram-Negative Bacteria - drug effects; Gram-Negative Bacteria - metabolism; Humans; Membrane Transport Proteins - chemistry; Membrane Transport Proteins - metabolism; Nodulation; Protein transport; Pumps; Review; Structural Biology; Structure-Activity Relationship; Structure-function relationships
• ISSN: 1092-2172; 1098-5557; 1098-5557
• DOI: 10.1128/mmbr.00089-23

SUMMARYThe discovery of bacterial efflux pumps significantly advanced our understanding of how bacteria can resist cytotoxic compounds that they encounter. Within the structurally and functionally distinct families of efflux pumps, those of the Resistance-Nodulation-Division (RND) superfamily are noteworthy for their ability to reduce the intracellular concentration of structurally diverse antimicrobials. RND systems are possessed by many Gram-negative bacteria, including those causing serious human disease, and frequently contribute to resistance to multiple antibiotics. Herein, we review the current literature on the structure-function relationships of representative transporter proteins of tripartite RND efflux pumps of clinically important pathogens. We emphasize their contribution to bacterial resistance to clinically used antibiotics, host defense antimicrobials and other biocides, as well as highlighting structural similarities and differences among efflux transporters that help bacteria survive in the face of antimicrobials. Furthermore, we discuss technical advances that have facilitated and advanced efflux pump research and suggest future areas of investigation that will advance antimicrobial development efforts.