{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:45:39Z","timestamp":1791179139979,"version":"4.1.0"},"reference-count":40,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[1999,2,1]],"date-time":"1999-02-01T00:00:00Z","timestamp":917827200000},"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":[[1999,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>During a 6-month period, 21 pairs of<jats:italic>Pseudomonas aeruginosa<\/jats:italic>isolates susceptible (pretherapy) and resistant (posttherapy) to antipseudomonal \u03b2-lactam antibiotics were isolated from hospitalized patients. In vivo emergence of \u03b2-lactam resistance was associated with the overexpression of AmpC \u03b2-lactamase in 10 patients. In the other 11 patients, the posttherapy isolates produced only low, basal levels of \u03b2-lactamase and had increased levels of resistance to a variety of non-\u03b2-lactam antibiotics (e.g., quinolones, tetracyclines, and trimethoprim) compared with the levels of \u03b2-lactamase production and resistance of their pretherapy counterparts. These data suggested the involvement of the MexA-MexB-OprM active efflux system in the multidrug resistance phenotype of the posttherapy strains. Immunoblotting of the outer membrane proteins of these 11 bacterial pairs with a specific polyclonal antibody raised against OprM demonstrated the overexpression of OprM in all the posttherapy isolates. To determine whether mutations in<jats:italic>mexR<\/jats:italic>, the regulator gene of the<jats:italic>mexA-mexB-oprM<\/jats:italic>efflux operon, could account for the overproduction of the efflux system, sequencing experiments were carried out with the 11 bacterial pairs. Eight posttherapy isolates were found to contain insertions or deletions that led to frameshifts in the coding sequences of<jats:italic>mexR<\/jats:italic>. Two resistant strains had point mutations in<jats:italic>mexR<\/jats:italic>that yielded single amino acid changes in the protein MexR, while another strain did not show any mutation in<jats:italic>mexR<\/jats:italic>or in the promoter region upstream of<jats:italic>mexR<\/jats:italic>. Introduction of a plasmid-encoded wild-type<jats:italic>mexR<\/jats:italic>gene into five posttherapy isolates partially restored the susceptibility of the bacteria to selected antibiotics. These results indicate that in the course of antimicrobial therapy multidrug-resistant active efflux mutants overexpressing the MexA-MexB-OprM system may emerge as a result of mutations in the<jats:italic>mexR<\/jats:italic>gene.<\/jats:p>","DOI":"10.1128\/aac.43.2.287","type":"journal-article","created":{"date-parts":[[2018,10,9]],"date-time":"2018-10-09T00:34:13Z","timestamp":1539045253000},"page":"287-291","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":222,"title":["In Vivo Emergence of Multidrug-Resistant Mutants of<i>Pseudomonas aeruginosa<\/i>Overexpressing the Active Efflux System MexA-MexB-OprM"],"prefix":"10.1128","volume":"43","author":[{"given":"Isabelle","family":"Ziha-Zarifi","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Laboratoire de Bacte\u0301riologie, Ho\u0302pital Jean Minjoz, F-25030 Besanc\u0327on, France,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Llanes","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Laboratoire de Bacte\u0301riologie, Ho\u0302pital Jean Minjoz, F-25030 Besanc\u0327on, France,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thilo","family":"Ko\u0308hler","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Department of Genetics and Microbiology, Centre Me\u0301dical Universitaire, CH-1211 Geneva 4, Switzerland2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Claude","family":"Pechere","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Department of Genetics and Microbiology, Centre Me\u0301dical Universitaire, CH-1211 Geneva 4, Switzerland2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Plesiat","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Laboratoire de Bacte\u0301riologie, Ho\u0302pital Jean Minjoz, F-25030 Besanc\u0327on, France,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(05)80360-2"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","unstructured":"Balows A. 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