{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:03:26Z","timestamp":1791237806135,"version":"4.1.0"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2008,5,1]],"date-time":"2008-05-01T00:00:00Z","timestamp":1209600000000},"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":[[2008,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    One way to combat multidrug-resistant microorganisms is the use of efflux pump inhibitors (EPIs). Spontaneous mutants resistant to the EPI reserpine selected from\n                    <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n                    NCTC 7465 and R6 at a frequency suggestive of a single mutational event were also multidrug resistant. No mutations in\n                    <jats:italic>pmrA<\/jats:italic>\n                    (which encodes the efflux protein PmrA) were detected, and the expression of\n                    <jats:italic>pmrA<\/jats:italic>\n                    was unaltered in all mutants. In the reserpine-resistant multidrug-resistant mutants, the overexpression of both\n                    <jats:italic>patA<\/jats:italic>\n                    and\n                    <jats:italic>patB<\/jats:italic>\n                    , which encode ABC transporters, was associated with accumulation of low concentrations of antibiotics and dyes. The addition of sodium orthovanadate, an inhibitor of ABC efflux pumps, or the insertional inactivation of either gene restored wild-type antibiotic susceptibility and wild-type levels of accumulation. Only when\n                    <jats:italic>patA<\/jats:italic>\n                    was insertionally inactivated were both multidrug resistance and reserpine resistance lost. Strains in which\n                    <jats:italic>patA<\/jats:italic>\n                    was insertionally inactivated grew significantly more slowly than the wild type. These data indicate that the overexpression of both\n                    <jats:italic>patA<\/jats:italic>\n                    and\n                    <jats:italic>patB<\/jats:italic>\n                    confers multidrug resistance in\n                    <jats:italic>S. pneumoniae<\/jats:italic>\n                    but that only\n                    <jats:italic>patA<\/jats:italic>\n                    is involved in reserpine resistance. The selection of reserpine-resistant multidrug-resistant pneumococci has implications for analogous systems in other bacteria or in cancer.\n                  <\/jats:p>","DOI":"10.1128\/aac.01644-07","type":"journal-article","created":{"date-parts":[[2008,3,24]],"date-time":"2008-03-24T20:26:22Z","timestamp":1206390382000},"page":"1677-1685","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":95,"title":["The Efflux Pump Inhibitor Reserpine Selects Multidrug-Resistant\n                    <i>Streptococcus pneumoniae<\/i>\n                    Strains That Overexpress the ABC Transporters PatA and PatB"],"prefix":"10.1128","volume":"52","author":[{"given":"Mark I.","family":"Garvey","sequence":"first","affiliation":[{"name":"Antimicrobial Agents Research Group, Division of Immunity and Infection, The Medical School, University of Birmingham, Birmingham, United Kingdom B15 2TT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura J. 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