{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T04:02:26Z","timestamp":1789531346313,"version":"build-2803163510"},"reference-count":53,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2017,2,1]],"date-time":"2017-02-01T00:00:00Z","timestamp":1485907200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"JSPS KAKENHI","award":["15H06521"],"award-info":[{"award-number":["15H06521"]}]},{"name":"JSPS KAKENHI","award":["25861574"],"award-info":[{"award-number":["25861574"]}]},{"name":"Yuasa Memorial Foundation"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Tigecycline (TGC) is a last-line drug for multidrug-resistant\n                    <jats:named-content content-type=\"genus-species\">Enterobacteriaceae<\/jats:named-content>\n                    . We investigated the mechanism(s) underlying TGC nonsusceptibility (TGC resistant\/intermediate) in\n                    <jats:named-content content-type=\"genus-species\">Escherichia coli<\/jats:named-content>\n                    clinical isolates. The MIC of TGC was determined for 277 fluoroquinolone-susceptible isolates (ciprofloxacin [CIP] MIC, &lt;0.125 mg\/liter) and 194 fluoroquinolone-resistant isolates (CIP MIC, &gt;2 mg\/liter). The MIC\n                    <jats:sub>50<\/jats:sub>\n                    and MIC\n                    <jats:sub>90<\/jats:sub>\n                    for TGC in fluoroquinolone-resistant isolates were 2-fold higher than those in fluoroquinolone-susceptible isolates (MIC\n                    <jats:sub>50<\/jats:sub>\n                    , 0.5 mg\/liter versus 0.25 mg\/liter; MIC\n                    <jats:sub>90<\/jats:sub>\n                    , 1 mg\/liter versus 0.5 mg\/liter, respectively). Two fluoroquinolone-resistant isolates (O25b:H4-ST131-\n                    <jats:italic>H<\/jats:italic>\n                    30R and O125:H37-ST48) were TGC resistant (MICs of 4 and 16 mg\/liter, respectively), and four other isolates of O25b:H4-ST131-\n                    <jats:italic>H<\/jats:italic>\n                    30R and an isolate of O1-ST648 showed an intermediate interpretation (MIC, 2 mg\/liter). No TGC-resistant\/intermediate strains were found among the fluoroquinolone-susceptible isolates. The TGC-resistant\/intermediate isolates expressed higher levels of\n                    <jats:italic>acrA<\/jats:italic>\n                    and\n                    <jats:italic>acrB<\/jats:italic>\n                    and had lower intracellular TGC concentrations than susceptible isolates, and they possessed mutations in\n                    <jats:italic>acrR<\/jats:italic>\n                    and\/or\n                    <jats:italic>marR<\/jats:italic>\n                    . The MICs of\n                    <jats:italic>acrAB<\/jats:italic>\n                    -deficient mutants were markedly lower (0.25 mg\/liter) than those of the parental strain. After continuous stepwise exposure to CIP\n                    <jats:italic>in vitro<\/jats:italic>\n                    , six of eight TGC-susceptible isolates had reduced TGC susceptibility. Two of them acquired TGC resistance (TGC MIC, 4 mg\/liter) and exhibited expression of\n                    <jats:italic>acrA<\/jats:italic>\n                    and\n                    <jats:italic>acrB<\/jats:italic>\n                    and mutations in\n                    <jats:italic>acrR<\/jats:italic>\n                    and\/or\n                    <jats:italic>marR<\/jats:italic>\n                    . In conclusion, a population of fluoroquinolone-resistant\n                    <jats:named-content content-type=\"genus-species\">E. coli<\/jats:named-content>\n                    isolates, including major extraintestinal pathogenic lineages O25b:H4-ST131-\n                    <jats:italic>H<\/jats:italic>\n                    30R and O1-ST648, showed reduced susceptibility to TGC due to overexpression of the efflux pump AcrAB-TolC, leading to decreased intracellular concentrations of the antibiotics that may be associated with the development of fluoroquinolone resistance.\n                  <\/jats:p>","DOI":"10.1128\/aac.01654-16","type":"journal-article","created":{"date-parts":[[2016,11,14]],"date-time":"2016-11-14T21:50:38Z","timestamp":1479160238000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":23,"title":["Tigecycline Nonsusceptibility Occurs Exclusively in Fluoroquinolone-Resistant Escherichia coli Clinical Isolates, Including the Major Multidrug-Resistant Lineages O25b:H4-ST131-H\n                    <i>30<\/i>\n                    R and O1-ST648"],"prefix":"10.1128","volume":"61","author":[{"given":"Toyotaka","family":"Sato","sequence":"first","affiliation":[{"name":"Department of Microbiology, Sapporo Medical University School of Medicine, Sapporo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuuki","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Sapporo Medical University School of Medicine, Sapporo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsukasa","family":"Shiraishi","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Sapporo Medical University School of Medicine, Sapporo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Honda","sequence":"additional","affiliation":[{"name":"Department of Microbiology, 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