{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T23:02:03Z","timestamp":1770073323738,"version":"3.49.0"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2014,10,1]],"date-time":"2014-10-01T00:00:00Z","timestamp":1412121600000},"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":[[2014,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Tigecycline nonsusceptibility is concerning because tigecycline is increasingly relied upon to treat carbapenem- or colistin-resistant organisms. In\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Enterobacteriaceae<\/jats:named-content>\n            , tigecycline nonsusceptibility is mediated by the AcrAB-TolC efflux pump, among others, and pump activity is often a downstream effect of mutations in their transcriptional regulators, cognate repressor genes, or noncoding regions, as demonstrated in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Enterobacteriaceae<\/jats:named-content>\n            and\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Acinetobacter<\/jats:named-content>\n            isolates. Here, we report the emergence of tigecycline nonsusceptibility in a longitudinal series of multidrug-resistant (MDR) and extensively drug-resistant (XDR)\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Klebsiella pneumoniae<\/jats:named-content>\n            isolates collected during tigecycline therapy and the elucidation of its resistance mechanisms. Clinical isolates were recovered prior to and during tigecycline therapy of a 2.5-month-old Honduran neonate. Antimicrobial susceptibility tests to tigecycline determined that the MIC increased from 1 to 4 \u03bcg\/ml prior to the completion of tigecycline therapy. Unlike other studies, we did not find increased expression of\n            <jats:italic>ramA<\/jats:italic>\n            ,\n            <jats:italic>ramR<\/jats:italic>\n            ,\n            <jats:italic>oqxA<\/jats:italic>\n            ,\n            <jats:italic>acrB<\/jats:italic>\n            ,\n            <jats:italic>marA<\/jats:italic>\n            , or\n            <jats:italic>rarA<\/jats:italic>\n            genes by reverse transcription-quantitative PCR (qRT-PCR). Whole-genome sequencing revealed an IS\n            <jats:italic>5<\/jats:italic>\n            insertion element in nonsusceptible isolates 85 bp upstream of a putative efflux pump operon, here named\n            <jats:italic>kpgABC<\/jats:italic>\n            , previously unknown to be involved in resistance. Introduction of the\n            <jats:italic>kpgABC<\/jats:italic>\n            genes in a non-\n            <jats:italic>kpgABC<\/jats:italic>\n            background increased the MIC of tigecycline 4-fold and is independent of a functional AcrAB-TolC pump. This is the first report to propose a function for\n            <jats:italic>kpgABC<\/jats:italic>\n            and identify an insertion element whose presence correlated with the\n            <jats:italic>in vivo<\/jats:italic>\n            development of tigecycline nonsusceptibility in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">K. pneumoniae<\/jats:named-content>\n            .\n          <\/jats:p>","DOI":"10.1128\/aac.03053-14","type":"journal-article","created":{"date-parts":[[2014,8,5]],"date-time":"2014-08-05T03:35:46Z","timestamp":1407209746000},"page":"6151-6156","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":53,"title":["IS\n            <i>5<\/i>\n            Element Integration, a Novel Mechanism for Rapid\n            <i>In Vivo<\/i>\n            Emergence of Tigecycline Nonsusceptibility in Klebsiella pneumoniae"],"prefix":"10.1128","volume":"58","author":[{"given":"Lindsey E.","family":"Nielsen","sequence":"first","affiliation":[{"name":"Multidrug-Resistant Organism Repository and Surveillance Network (MRSN), Walter Reed Army Institute of Research, Silver Spring, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik C.","family":"Snesrud","sequence":"additional","affiliation":[{"name":"Multidrug-Resistant Organism Repository and Surveillance Network (MRSN), Walter Reed Army Institute of Research, Silver Spring, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatma","family":"Onmus-Leone","sequence":"additional","affiliation":[{"name":"Multidrug-Resistant Organism Repository and Surveillance Network (MRSN), Walter Reed Army Institute of Research, Silver Spring, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoon I.","family":"Kwak","sequence":"additional","affiliation":[{"name":"Multidrug-Resistant Organism Repository and Surveillance Network (MRSN), Walter Reed Army Institute of Research, Silver Spring, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo","family":"Avil\u00e9s","sequence":"additional","affiliation":[{"name":"Soto Cano Air Base, Comayagua, Honduras"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric D.","family":"Steele","sequence":"additional","affiliation":[{"name":"MRSN, San Antonio Military Medical Center, Fort Sam Houston, San Antonio, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deena E.","family":"Sutter","sequence":"additional","affiliation":[{"name":"Division of Pediatric Infectious Disease, San Antonio Military Medical Center, Fort Sam Houston, San Antonio, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paige 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