Comparative genomic analysis of plasmids harboring blaOXA-48-like genes in Klebsiella pneumoniae

The emergence and spread of carbapenem-resistant Klebsiella pneumoniae (CRKP) is a serious medical problem worldwide. Acquired OXA-48-like carbapenemases encoded by plasmids are important causes of carbapenem resistance in K. pneumoniae. To explore the links between plasmids and bla(OXA-48)-like genes in K. pneumoniae, we systematically analyzed the variants of bla(OXA-48)-like plasmid replicon types, phylogenetic patterns, geographic distribution, conjugative transfer regions, and the genetic environments surrounding bla(OXA-48)-like of 191 bla(OXA-48)-like-harboring plasmids, which were identified from 4451 plasmids of K. pneumoniae downloaded from GenBank. Our results showed that seven different variants of bla(OXA-48)-like genes were identified from the 191 bla(OXA-48)-like-harboring plasmids in K. pneumoniae, with bla(OXA-48), bla(OXA-232), and bla(OXA-181) being highly prevalent. In K. pneumoniae, bla(OXA-48) was mainly carried by the composite transposon Tn1999.2 located on IncL/M-type conjugative plasmids, which were mainly geographically distributed in Switzerland, Germany, and China. In K. pneumoniae, the bla(OXA-232) gene was mainly carried by 6.1-kb ColKP3-type mobilizable plasmids, which were mainly isolated in India. In K. pneumoniae, bla(OXA-181) was mainly carried by a group of 50-kb ColKP3-IncX3 hybrid conjugative plasmids and a group of small ColKP3-type mobilizable plasmids with lengths of 5.9-9.3 kb, the former was sporadically discovered in China, South Korea, India, and Czech Republic, while the latter was almost all isolated in India. In addition, five bla(OXA-245)-harboring 65.9-kb IncL plasmids of K. pneumoniae isolated in Spain were found to have the genetic context of bla(OXA-245) more complicated than that of bla(OXA-48)-harboring IncL/M-type plasmids, with two copies of IS1R inserted both upstream and downstream of bla(OXA-245)-lysR. These findings enhance our understanding of the genetic diversity of bla(OXA-48)-like-harboring plasmids in K. pneumoniae.

Automated summary

This study systematically analyzed the characteristics of 191 plasmids carrying bla(OXA-48)-like genes in K. pneumoniae. Multiple variants of bla(OXA-48)-like genes were identified, and their high prevalence, geographic distribution, and plasmid types were determined.