Genetic characteristics of OXA-48-producing Enterobacterales from China

Abstract

In China, OXA-48-producing Enterobacterales have been identified sporadically, causing small-scale regional outbreaks. This study investigated the molecular epidemiology, transmission and evolution of OXA-48-producing Enterobacterales and pOXA48 from mainland China. We conducted a multicentre resistance monitoring project from 2013-2018. Genome sequencing of OXA-48-produicng isolates was performed. SNPs were analysed. Eleven isolates were selected for subsequent SMRT sequencing. Genome sequences were annotated, and alignment of the complete sequences of blaOXA-48-carrying plasmids from a subset of isolates that underwent long-read sequencing was performed. In total, 41 OXA-48-producing Enterobacterales were included in this study (34 Klebsiella pneumoniae, 3 Escherichia coli, 3 Enterobacter cloacae complex and 1 Klebsiella oxytoca). OXA-48-produicng K. pneumoniae (OXAKp) ST383, ST147 and ST11 caused outbreaks of different scales in our hospital. OXA-48-producing E. coli ST156 and ST648, E. cloacae complex ST414 and ST418, and K. oxytoca ST34 were also identified. blaOXA-48 was embedded in a Tn1999.2 structure located in IncL plasmids with different sizes (63.58-109.14 kb). Importantly, K. pneumoniae ST11 co-producing KPC-2 and OXA-48 was identified in our hospital and it is possible that KPC-2-producing K. pneumoniae ST11 obtained the blaOXA-48-carrying plasmid during its spread. A novel 109-kb blaOXA-48-carrying IncL plasmid was identified from OXAKp ST11. Possibly, two plasmids in OXAKp ST383 were integrated to form this larger plasmid. OXA-48-produicng Enterobacterales were sporadic in China. Importantly, K. pneumoniae ST11 co-producing KPC-2 and OXA-48 has emerged causing an outbreak in China. This high-risk multidrug-resistant clone exhibited high compatibility and strong integration ability with foreign resistance plasmids.