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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.<\/jats:p>","DOI":"10.1128\/mmbr.00089-23","type":"journal-article","created":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T09:02:47Z","timestamp":1725526967000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":40,"title":["Structural and functional diversity of Resistance-Nodulation-Division (RND) efflux pump transporters with implications for antimicrobial resistance"],"prefix":"10.1128","volume":"88","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9467-7175","authenticated-orcid":false,"given":"Logan G.","family":"Kavanaugh","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA"},{"name":"Graduate Program in Microbiology and Molecular Genetics, Emory University, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0222-6092","authenticated-orcid":false,"given":"Debayan","family":"Dey","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9303-8777","authenticated-orcid":true,"given":"William M.","family":"Shafer","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA"},{"name":"Laboratories of Microbial Pathogenesis, VA Medical Research Service, Veterans Affairs Medical Center, Decatur, Georgia, USA"},{"name":"Emory Antibiotic Resistance Center, Emory University School of Medicine, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2419-380X","authenticated-orcid":true,"given":"Graeme L.","family":"Conn","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA"},{"name":"Emory Antibiotic Resistance Center, Emory University School of Medicine, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","unstructured":"Penicillin FA. 1945. 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