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<jats:title>ABSTRACT</jats:title> <jats:p> Carbapenemase genes in <jats:named-content content-type="genus-species">Enterobacteriaceae</jats:named-content> are mostly described as being plasmid associated. However, the genetic context of carbapenemase genes is not always confirmed in epidemiological surveys, and the frequency of their chromosomal integration therefore is unknown. A previously sequenced collection of <jats:italic>bla</jats:italic> <jats:sub>KPC</jats:sub> -positive <jats:named-content content-type="genus-species">Enterobacteriaceae</jats:named-content> from a single U.S. institution (2007 to 2012; <jats:italic>n</jats:italic> = 281 isolates from 182 patients) was analyzed to identify chromosomal insertions of Tn <jats:italic>4401</jats:italic> , the transposon most frequently harboring <jats:italic>bla</jats:italic> <jats:sub>KPC</jats:sub> . Using a combination of short- and long-read sequencing, we confirmed five independent chromosomal integration events from 6/182 (3%) patients, corresponding to 15/281 (5%) isolates. Three patients had isolates identified by perirectal screening, and three had infections which were all successfully treated. When a single copy of <jats:italic>bla</jats:italic> <jats:sub>KPC</jats:sub> was in the chromosome, one or both of the phenotypic carbapenemase tests were negative. All chromosomally integrated <jats:italic>bla</jats:italic> <jats:sub>KPC</jats:sub> genes were from <jats:named-content content-type="genus-species">Klebsiella</jats:named-content> spp., predominantly <jats:named-content content-type="genus-species">K. pneumoniae</jats:named-content> clonal group 258 (CG258), even though these represented only a small proportion of the isolates. Integration occurred via IS <jats:italic>15</jats:italic> -ΔI-mediated transposition of a larger, composite region encompassing Tn <jats:italic>4401</jats:italic> at one locus of chromosomal integration, seen in the same strain ( <jats:named-content content-type="genus-species">K. pneumoniae</jats:named-content> ST340) in two patients. In summary, we identified five independent chromosomal integrations of <jats:italic>bla</jats:italic> <jats:sub>KPC</jats:sub> in a large outbreak, demonstrating that this is not a rare event. <jats:italic>bla</jats:italic> <jats:sub>KPC</jats:sub> was more frequently integrated into the chromosome of epidemic CG258 <jats:named-content content-type="genus-species">K. pneumoniae</jats:named-content> lineages (ST11, ST258, and ST340) and was more difficult to detect by routine phenotypic methods in this context. The presence of chromosomally integrated <jats:italic>bla</jats:italic> <jats:sub>KPC</jats:sub> within successful, globally disseminated <jats:named-content content-type="genus-species">K. pneumoniae</jats:named-content> strains therefore is likely underestimated. </jats:p>

Original publication




Journal article


Antimicrobial Agents and Chemotherapy


American Society for Microbiology

Publication Date