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<jats:p>The recent widespread emergence of carbapenem resistance in<jats:named-content content-type="genus-species">Enterobacteriaceae</jats:named-content>is a major public health concern, as carbapenems are a therapy of last resort against this family of common bacterial pathogens. Resistance genes can mobilize via various mechanisms, including conjugation and transposition; however, the importance of this mobility in short-term evolution, such as within nosocomial outbreaks, is unknown. Using a combination of short- and long-read whole-genome sequencing of 281<jats:italic>bla</jats:italic><jats:sub>KPC</jats:sub>-positive<jats:named-content content-type="genus-species">Enterobacteriaceae</jats:named-content>isolates from a single hospital over 5 years, we demonstrate rapid dissemination of this carbapenem resistance gene to multiple species, strains, and plasmids. Mobility of<jats:italic>bla</jats:italic><jats:sub>KPC</jats:sub>occurs at multiple nested genetic levels, with transmission of<jats:italic>bla</jats:italic><jats:sub>KPC</jats:sub>strains between individuals, frequent transfer of<jats:italic>bla</jats:italic><jats:sub>KPC</jats:sub>plasmids between strains/species, and frequent transposition of<jats:italic>bla</jats:italic><jats:sub>KPC</jats:sub>transposon Tn<jats:italic>4401</jats:italic>between plasmids. We also identify a common insertion site for Tn<jats:italic>4401</jats:italic>within various Tn<jats:italic>2</jats:italic>-like elements, suggesting that homologous recombination between Tn<jats:italic>2</jats:italic>-like elements has enhanced the spread of Tn<jats:italic>4401</jats:italic>between different plasmid vectors. Furthermore, while short-read sequencing has known limitations for plasmid assembly, various studies have attempted to overcome this by the use of reference-based methods. We also demonstrate that, as a consequence of the genetic mobility observed in this study, plasmid structures can be extremely dynamic, and therefore these reference-based methods, as well as traditional partial typing methods, can produce very misleading conclusions. Overall, our findings demonstrate that nonclonal resistance gene dissemination can be extremely rapid, presenting significant challenges for public health surveillance and achieving effective control of antibiotic resistance.</jats:p>

Original publication

DOI

10.1128/aac.00464-16

Type

Journal article

Journal

Antimicrobial Agents and Chemotherapy

Publisher

American Society for Microbiology

Publication Date

06/2016

Volume

60

Pages

3767 - 3778