{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T17:41:51Z","timestamp":1784655711864,"version":"3.55.0"},"reference-count":15,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2019,5,25]],"date-time":"2019-05-25T00:00:00Z","timestamp":1558742400000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100007921","name":"University of Pittsburgh","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007921","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["K08AI114883"],"award-info":[{"award-number":["K08AI114883"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01GM110444"],"award-info":[{"award-number":["R01GM110444"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["U01AI124302"],"award-info":[{"award-number":["U01AI124302"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01AI104895"],"award-info":[{"award-number":["R01AI104895"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R21AI123747"],"award-info":[{"award-number":["R21AI123747"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R21AI135522"],"award-info":[{"award-number":["R21AI135522"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>OXA-2 is a class D \u03b2-lactamase that confers resistance to penicillins, as well as narrow-spectrum cephalosporins. OXA-2 was recently reported to also possess carbapenem-hydrolysing activity. Here, we describe a KPC-2-encoding Klebsiella pneumoniae isolate that demonstrated reduced susceptibility to ceftazidime and ertapenem due to production of OXA-2.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To elucidate the role of OXA-2 production in reduced ceftazidime and ertapenem susceptibility in a K. pneumoniae ST258 clinical isolate.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>MICs were determined by the agar dilution method. WGS was conducted to identify and compare resistance genes between isolates. Expression of KPC-2 was quantified by quantitative RT\u2013PCR and immunoblotting. OXA-2 was expressed in Escherichia coli TOP10, as well as in K. pneumoniae ATCC 13883, to define the relative contribution of OXA-2 in \u03b2-lactam resistance. Kinetic studies were conducted using purified OXA-2 enzyme.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>K. pneumoniae 1761 belonged to ST258 and carried both blaKPC-2 and blaOXA-2. However, expression of blaKPC-2 was substantially reduced due to an IS1294 insertion in the promoter region. K. pneumoniae 1761, K. pneumoniae ATCC 13883 and E. coli TOP10 carrying blaOXA-2-harbouring plasmids showed reduced susceptibility to ertapenem and ceftazidime, but meropenem, imipenem and cefepime were unaffected. blaOXA-2 was carried on a 2910\u2009bp partial class 1 integron containing aacA4-blaOXA-2-qacE\u03941-sul1 on an IncA\/C2 plasmid, which was not present in the earlier ST258 isolates possessing blaKPC-2 with intact promoters. Hydrolysis of ertapenem by OXA-2 was confirmed using purified enzyme.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Production of OXA-2 was associated with reduced ceftazidime and ertapenem susceptibility in a K. pneumoniae ST258 isolate.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkz183","type":"journal-article","created":{"date-parts":[[2019,4,25]],"date-time":"2019-04-25T15:12:33Z","timestamp":1556205153000},"page":"2203-2208","source":"Crossref","is-referenced-by-count":7,"title":["Reduced ceftazidime and ertapenem susceptibility due to production of OXA-2 in Klebsiella pneumoniae ST258"],"prefix":"10.1093","volume":"74","author":[{"given":"Alina","family":"Iovleva","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta T","family":"Mettus","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christi L","family":"McElheny","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustapha M","family":"Mustapha","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"},{"name":"Center for Innovative Antimicrobial Therapy, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Van Tyne","sequence":"additional","affiliation":[{"name":"Division 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University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"},{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohei","family":"Doi","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"},{"name":"Center for Innovative Antimicrobial Therapy, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"},{"name":"Departments of Microbiology and Infectious Diseases, Fujita Health University School of Medicine, Toyoake, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,5,24]]},"reference":[{"key":"2019071909304556000_dkz183-B1","doi-asserted-by":"crossref","first-page":"398","DOI":"10.3390\/antibiotics3030398","article-title":"Acquired class D 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