TY - JOUR T1 - Genomic investigation of an outbreak of carbapenemase-producing <em>Enterobacter cloacae:</em> long-read sequencing reveals the context of <em>bla</em>IMP4 on a widely distributed IncHI2 plasmid JF - bioRxiv DO - 10.1101/172536 SP - 172536 AU - Leah W. Roberts AU - Patrick N. A. Harris AU - Nouri L. Ben Zakour AU - Brian M. Forde AU - Elizabeth Catchpoole AU - Mitchell Stanton-Cook AU - Minh-Duy Phan AU - Hanna Sidjabat AU - Haakon Bergh AU - Claire Heney AU - Jayde A. Gawthorne AU - Jeffrey Lipman AU - Anthony Allworth AU - Kok-Gan Chan AU - Teik Min Chong AU - Wai-Fong Yin AU - Mark A. Schembri AU - David L. Paterson AU - Scott A. Beatson Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/08/04/172536.abstract N2 - Background We describe whole genome sequencing (WGS) to analyse a cluster of blaIMP-4 carbapenemase-producing Enterobacter cloacae.Methods A cluster of carbapenemase-producing E. cloacae were identified over a two month period in 2015 within an Intensive Care Unit (ICU)/Burns Unit in Brisbane, Australia. Phylogenetic relationships based on core single nucleotide polymorphisms (SNPs) were determined using WGS. Genomic comparisons were made to IMP-producing Enterobacteriaceae from neighbouring hospitals and to publicly available genomes to contextualise the isolates in the broader community. Pacific Biosciences Single Molecule Real-Time (SMRT) sequencing of one IMP-4-producing E. cloacae strain was used to resolve the full context of the resistance genes.Results All outbreak strains were sequence type 90 and differed by only four core SNPs. WGS analysis unequivocally linked all 10 isolates to a 2013 isolate from the same ward, confirming the hospital environment as the most likely original source of infection in the 2015 cases. No clonal relationship was found to IMP-4-producing isolates identified from other local hospitals. However, all IMP-4-producing strains were found to possess an identical blaIMP-4 carried on a large IncHI2 plasmid.Conclusions During the course of an outbreak investigation, WGS revealed the transmission dynamics of a carbapenemase-producing E. cloacae cluster, linking it to a historical isolate from the same Unit and revealing the full context of blaIMP-4 on a multi-drug resistant IncHI2 plasmid that appears to be widely distributed in Australia.40-word summary Whole genome sequencing of blaIMP-4-producing Enterobacter cloacae detected an unknown persistent source of infection within the hospital. All isolates were found to carry multiple antibiotic resistance genes, located in a large multidrug resistant region on a 330,060 bp IncHI2 plasmid. ER -