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

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 no...

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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
Bacteria - drug effects
Bacteria - metabolism
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Drug Resistance, Bacterial
Drug Resistance, Multiple, Bacterial
Gram-Negative Bacteria - drug effects
Gram-Negative Bacteria - metabolism
Humans
Membrane Transport Proteins - chemistry
Membrane Transport Proteins - metabolism
Review
Structural Biology
Structure-Activity Relationship
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Summary: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.
ISSN:1092-2172
1098-5557
1098-5557
DOI:10.1128/mmbr.00089-23