IncN ST7 epidemic plasmid carrying blaIMP-4 in Enterobacteriaceae isolates with epidemiological links to multiple geographical areas in China

Objectives: To characterize bla(IMP-4)-carrying plasmids originating from inpatients in Hong Kong. Methods: Sixteen blaIMP-4-carrying plasmids identified among Enterobacteriaceae (nine Escherichia coli, four Klebsiella pneumoniae, two Citrobacter freundii and one Enterobacter cloacae) recovered from 15 patients were characterized. The isolates, collected during January 2010 to December 2013, were retrospectively investigated by plasmid sequencing, molecular and fitness studies. Results: The blaIMP-4-carrying plasmids belonged to the IncN ST7 lineage (similar to 50kb). Twelve of the 16 plasmids were epidemiologically linked to seven different regions in China. Alignment of the complete plasmid sequences showed identical plasmid backbones and two highly similar resistance regions, each carrying one of two resistance genes (bla(IMP-4) and qnrS1). The blaIMP-4 was detected in a class 1 integron (containing blaIMP-4 and intron Kl. pn. 13) that is part of an IS6100-IS26 transposon-like structure. The nine E. coli carrying the epidemic plasmid belonged to multiple multilocus STs (six ST542, one ST131, one ST657 and one ST3177). Fitness assays performed on E. coli J53 recipients showed that the presence of the epidemic plasmid did not have a significant biological cost. Conclusions: This study identified a blaIMP-4-carrying IncN ST7 plasmid disseminated amongmultiple enterobacterial species originating from patients with epidemiological links to different regions in China.