{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T01:07:42Z","timestamp":1791248862006,"version":"4.1.0"},"reference-count":61,"publisher":"Rockefeller University Press","issue":"1","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,7,1]]},"abstract":"<jats:p>Pseudomonas aeruginosa is an important opportunistic human pathogen. Certain strains can transmigrate across epithelial cells, and their invasive phenotype is correlated with capacity to cause invasive human disease and fatal septicemia in mice. Four multidrug efflux systems have been described in P. aeruginosa, however, their contribution to virulence is unclear. To clarify the role of efflux systems in invasiveness, P. aeruginosa PAO1 wild-type (WT) and its efflux mutants were evaluated in a Madin-Darby canine kidney (MDCK) epithelial cell monolayer system and in a murine model of endogenous septicemia. All efflux mutants except a \u0394mexCD-oprJ deletion demonstrated significantly reduced invasiveness compared with WT. In particular, a \u0394mexAB-oprM deletion strain was compromised in its capacity to invade or transmigrate across MDCK cells, and could not kill mice, in contrast to WT which was highly invasive (P &amp;lt; 0.0006) and caused fatal infection (P &amp;lt; 0.0001). The other mutants, including \u0394mexB and \u0394mexXY mutants, were intermediate between WT and the \u0394mexAB-oprM mutant in invasiveness and murine virulence. Invasiveness was restored to the \u0394mexAB-oprM mutant by complementation with mexAB-oprM or by addition of culture supernatant from MDCK cells infected with WT. We conclude that the P. aeruginosa MexAB-OprM efflux system exports virulence determinants that contribute to bacterial virulence.<\/jats:p>","DOI":"10.1084\/jem.20020005","type":"journal-article","created":{"date-parts":[[2002,7,28]],"date-time":"2002-07-28T22:32:53Z","timestamp":1027895573000},"page":"109-118","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":224,"title":["Multidrug Efflux Systems Play an Important Role in the Invasiveness of <i>Pseudomonas aeruginosa <\/i>"],"prefix":"10.1084","volume":"196","author":[{"given":"Yoichi","family":"Hirakata","sequence":"first","affiliation":[{"name":"1Division of Infectious and Immunological Diseases, Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, V5Z 4H4 Canada"},{"name":"6Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, 852-8501 Japan"},{"name":"7Department of Laboratory Medicine, Nagasaki University School of Medicine, Nagasaki, 852-8501 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramakrishnan","family":"Srikumar","sequence":"additional","affiliation":[{"name":"2Department of Microbiology and Immunology, Queen's University, Kingston, Ontario K7L 3N6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Poole","sequence":"additional","affiliation":[{"name":"2Department of Microbiology and Immunology, Queen's University, Kingston, Ontario K7L 3N6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomasa","family":"Gotoh","sequence":"additional","affiliation":[{"name":"4Department of Microbiology, Kyoto Pharmaceutical University, Kyoto, 607-8414 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Suematsu","sequence":"additional","affiliation":[{"name":"5Central Electron Microscopy Laboratory, Nagasaki University School of Medicine, Nagasaki, 852-8501 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeru","family":"Kohno","sequence":"additional","affiliation":[{"name":"6Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, 852-8501 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimeru","family":"Kamihira","sequence":"additional","affiliation":[{"name":"7Department of Laboratory Medicine, Nagasaki University School of Medicine, Nagasaki, 852-8501 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert E. 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