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A highly related pair of\n            <jats:italic>K. pneumoniae<\/jats:italic>\n            strains isolated on the same day from one patient in a hospital in New York City were studied for antibiotic resistance. One (KP-2) was resistant to imipenem, meropenem, and sulopenem (MICs of 16 to 32 \u03bcg\/ml) while the other (KP-1) was susceptible (MIC of 0.5 \u03bcg\/ml); both contained the\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>ACT-1<\/jats:sub>\n            ,\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>SHV-1<\/jats:sub>\n            , and\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>TEM-1<\/jats:sub>\n            \u03b2-lactamases.\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>ACT-1<\/jats:sub>\n            in both strains was encoded on a large \u223c150-kb plasmid. Both isolates contained an identical class 1 integron encoding resistance to aminoglycosides and chloramphenicol. They each had identical insertions in\n            <jats:italic>ompK35<\/jats:italic>\n            and\n            <jats:italic>ompK36<\/jats:italic>\n            , resulting in disruption of these key porin genes. The carbapenem-resistant and -susceptible isolates were extensively studied for differences in the structural and regulatory genes for the operons\n            <jats:italic>acrRAB<\/jats:italic>\n            ,\n            <jats:italic>marORAB<\/jats:italic>\n            ,\n            <jats:italic>romA-ramA<\/jats:italic>\n            ,\n            <jats:italic>soxRS<\/jats:italic>\n            ,\n            <jats:italic>micF<\/jats:italic>\n            ,\n            <jats:italic>micC<\/jats:italic>\n            ,\n            <jats:italic>phoE<\/jats:italic>\n            ,\n            <jats:italic>phoBR<\/jats:italic>\n            ,\n            <jats:italic>rpoS<\/jats:italic>\n            , and\n            <jats:italic>hfq<\/jats:italic>\n            . No changes were detected between the isolates except for a significant down-regulation of\n            <jats:italic>ompK37<\/jats:italic>\n            ,\n            <jats:italic>phoB<\/jats:italic>\n            , and\n            <jats:italic>phoE<\/jats:italic>\n            in KP-2 as deduced from reverse transcription-PCR analysis of mRNA and polyacrylamide gel electrophoresis separation of outer membrane proteins. Backcross analysis was conducted using the wild-type\n            <jats:italic>phoE<\/jats:italic>\n            gene cloned into the vector pGEM under regulation of its native promoter as well as the\n            <jats:italic>lacZ<\/jats:italic>\n            promoter following transformation into the resistant KP-2 isolate. The wild-type gene reversed carbapenem resistance only when under control of the heterologous\n            <jats:italic>lacZ<\/jats:italic>\n            promoter. In the background of\n            <jats:italic>ompK35-ompK36<\/jats:italic>\n            gene disruption, the up-regulation of\n            <jats:italic>phoE<\/jats:italic>\n            in KP-1 apparently compensated for porin loss and conferred carbapenem susceptibility. Down-regulation of\n            <jats:italic>phoE<\/jats:italic>\n            in KP-2 may represent the normal state of this gene, or it may have been selected from KP-1 in vivo under antibiotic pressure, generating the carbapenem-resistant clone. This is the first study in the\n            <jats:italic>Enterobacteriaceae<\/jats:italic>\n            where expression of the phosphate-regulated PhoE porin has been associated with resistance to antimicrobials. Our results with this pair of\n            <jats:italic>Klebsiella<\/jats:italic>\n            clinical isolates highlight the complex and evolving nature of multiple drug resistance in this species.\n          <\/jats:p>","DOI":"10.1128\/aac.00285-06","type":"journal-article","created":{"date-parts":[[2006,9,27]],"date-time":"2006-09-27T17:13:29Z","timestamp":1159377209000},"page":"3396-3406","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":220,"title":["High-Level Carbapenem Resistance in a\n            <i>Klebsiella pneumoniae<\/i>\n            Clinical Isolate Is Due to the Combination of\n            <i>bla<\/i>\n            <sub>ACT-1<\/sub>\n            \u03b2-Lactamase Production, Porin OmpK35\/36 Insertional Inactivation, and Down-Regulation of the Phosphate Transport Porin PhoE"],"prefix":"10.1128","volume":"50","author":[{"given":"Frank M.","family":"Kaczmarek","sequence":"first","affiliation":[{"name":"Pfizer Global Research and Development, Groton, Connecticut 06340"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fadia","family":"Dib-Hajj","sequence":"additional","affiliation":[{"name":"Pfizer Global Research and Development, Groton, Connecticut 06340"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenchi","family":"Shang","sequence":"additional","affiliation":[{"name":"Pfizer Global Research and Development, Groton, Connecticut 06340"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas D.","family":"Gootz","sequence":"additional","affiliation":[{"name":"Pfizer Global Research and Development, Groton, Connecticut 06340"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2000.01802.x"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.10.2067"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.10.3303-3306.1999"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.7.1636"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.38.3.1048-1052.2000"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.6.2153-2158.2004"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1086\/421495"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.3.563"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.165.12.1430"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dki175"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.12.3739-3743.2002"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.24.3.330-332.1986"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2210505"},{"key":"e_1_3_2_15_2","unstructured":"Castanheira M. 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