{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T13:36:43Z","timestamp":1791466603793,"version":"4.3.4"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[1998,2,1]],"date-time":"1998-02-01T00:00:00Z","timestamp":886291200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[1998,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The MexAB-OprM multidrug efflux system exports a number of antimicrobial compounds, including \u03b2-lactams. In an attempt to define more fully the range of antimicrobial compounds exported by this system, and, in particular, to determine whether \u03b2-lactamase inhibitors were also accommodated by the MexAB-OprM pump, the influence of pump status (its presence or absence) on the intrinsic antibacterial activities of these compounds and on their abilities to enhance \u03b2-lactam susceptibility in intact cells was assessed. MIC determinations clearly demonstrated that all three compounds tested, clavulanate, cloxacillin, and BRL42715, were accommodated by the pump. Moreover, by using \u03b2-lactams which were readily hydrolyzed by the\n            <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n            class C chromosomal \u03b2-lactamase, it was demonstrated that elimination of the\n            <jats:italic>mexAB-oprM<\/jats:italic>\n            -encoded efflux system greatly enhanced the abilities of cloxacillin and BRL42715 (but not clavulanate) to increase \u03b2-lactam susceptibility. With \u03b2-lactams which were poorly hydrolyzed, however, the inhibitors failed to enhance \u03b2-lactam susceptibility in MexAB-OprM\n            <jats:sup>+<\/jats:sup>\n            strains, although BRL42715 did enhance \u03b2-lactam susceptibility in MexAB-OprM\n            <jats:sup>\u2212<\/jats:sup>\n            strains, suggesting that even with poorly hydrolyzed \u03b2-lactams this inhibitor was effective when it was not subjected to efflux. MexEF-OprN-overexpressing strains, but not MexCD-OprJ-overexpressing strains, also facilitated resistance to \u03b2-lactamase inhibitors, indicating that these compounds are also substrates for the MexEF-OprN pump. These data indicate that an ability to inactivate MexAB-OprM (and like efflux systems in other bacteria) will markedly enhance the efficacies of \u03b2-lactam\u2013\u03b2-lactamase inhibitor combinations in treating bacterial infections.\n          <\/jats:p>","DOI":"10.1128\/aac.42.2.399","type":"journal-article","created":{"date-parts":[[2020,4,3]],"date-time":"2020-04-03T16:19:43Z","timestamp":1585930783000},"page":"399-403","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":84,"title":["\u03b2-Lactamase Inhibitors Are Substrates for the Multidrug Efflux Pumps of\n            <i>Pseudomonas aeruginosa<\/i>"],"prefix":"10.1128","volume":"42","author":[{"given":"Xian-Zhi","family":"Li","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Department of Microbiology and Immunology, Queen\u2019s University, Kingston, Ontario K7L 3N6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Microbiology and Immunology, Queen\u2019s University, Kingston, Ontario K7L 3N6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramakrishnan","family":"Srikumar","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Microbiology and Immunology, Queen\u2019s University, Kingston, Ontario K7L 3N6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Poole","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Microbiology and Immunology, Queen\u2019s University, Kingston, Ontario K7L 3N6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1093\/infdis\/155.5.936","article-title":"Factors that influence the evolution of \u03b2-lactam resistance in \u03b2-lactamase-inducible strains of Enterobacter cloacae and Pseudomonas aeruginosa.","volume":"5","author":"Aranoff S. 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