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In the versatile, opportunistic pathogen\n              <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n              , the Resistance-Nodulation-Division (RND) efflux pump MexXY plays critical roles in both cell physiology and the acquisition of multidrug resistance. The\n              <jats:italic toggle=\"yes\">mexXY<\/jats:italic>\n              operon is not constitutively expressed, but this process is instead controlled by a complex network of multiple interconnected regulatory mechanisms. These include induction by several of the pump\u2019s ribosome-targeting antibiotic substrates and transcriptional repression and anti-repression processes that are themselves influenced by various cellular factors, processes, or stresses. Although extensive studies of the MexXY complex are currently lacking as compared to other RND efflux pumps such as\n              <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n              AcrAB-TolC, recent studies have provided valuable insights into the MexXY architecture and substrate profiles, including its contribution to clinical resistance. Furthermore, while MexXY primarily associates with the outer membrane protein OprM, emerging evidence suggests that this transporter-periplasmic adaptor pair may also partner with other outer membrane proteins, potentially to alter the efflux substrate profile and activity under specific environmental conditions. In this minireview, we summarize current understanding of MexXY regulation, structure, and substrate selectivity within the context of clinical resistance and as a framework for future efflux pump inhibitor development.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.01825-24","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T13:44:55Z","timestamp":1744033495000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["Regulation, structure, and activity of the\n            <i>Pseudomonas aeruginosa<\/i>\n            MexXY efflux system"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9467-7175","authenticated-orcid":true,"given":"Logan G.","family":"Kavanaugh","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Emory University School of Medicine","place":["Atlanta, USA"]},{"name":"Graduate Program in Microbiology and Molecular Genetics, Emory University","place":["Atlanta, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan E.","family":"Hinrichsen","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Emory University","place":["Atlanta, USA"]},{"name":"Graduate Program in Biochemistry, Cell and Developmental Biology, Emory University","place":["Atlanta, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8821-688X","authenticated-orcid":true,"given":"Christine M.","family":"Dunham","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Emory University","place":["Atlanta, USA"]},{"name":"Emory Antibiotic Resistance Center, Emory University School of Medicine","place":["Atlanta, 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","place":["Atlanta, USA"]},{"name":"Emory Antibiotic Resistance Center, Emory University School of Medicine","place":["Atlanta, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"National Center for E, zoonotic infectious diseases","author":"CDC","year":"2022","unstructured":"CDC. 2022. COVID-19: U.S. impact on antimicrobial resistance, special report 2022. In National Center for E, zoonotic infectious diseases. Division of Healthcare Quality Promotion, Atlanta, GA. https:\/\/stacks.cdc.gov\/view\/cdc\/119025."},{"key":"e_1_3_3_3_2","first-page":"277","volume-title":"Pharmacy and therapeutics","author":"Ventola CL","year":"2015","unstructured":"Ventola CL. 2015. The antibiotic resistance crisis, p 277\u2013283. In Pharmacy and therapeutics. 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