AUTHOR=Li Wang , Guo Hengzhao , Gao Yi , Yang Xiaofan , Li Ruirui , Li Shuangyu , Sun Chunlong , Du Wen , Chen Shaopeng , Xu Pengpeng , Huang Wenwen , Shi Jia , Yi Xinfeng , Li Xiaobin 

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

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.1082813

DOI=10.3389/fcimb.2022.1082813

ISSN=2235-2988

ABSTRACT=<p>The emergence and spread of carbapenem-resistant <italic>Klebsiella pneumoniae</italic> (CRKP) is a serious medical problem worldwide. Acquired OXA-48-like carbapenemases encoded by plasmids are important causes of carbapenem resistance in <italic>K. pneumoniae</italic>. To explore the links between plasmids and <italic>bla</italic><sub>OXA-48</sub>-like genes in <italic>K. pneumoniae</italic>, we systematically analyzed the variants of <italic>bla</italic><sub>OXA-48</sub>-like plasmid replicon types, phylogenetic patterns, geographic distribution, conjugative transfer regions, and the genetic environments surrounding <italic>bla</italic><sub>OXA-48</sub>-like of 191 <italic>bla</italic><sub>OXA-48</sub>-like-harboring plasmids, which were identified from 4451 plasmids of <italic>K. pneumoniae</italic> downloaded from GenBank. Our results showed that seven different variants of <italic>bla</italic><sub>OXA-48</sub>-like genes were identified from the 191 <italic>bla</italic><sub>OXA-48</sub>-like-harboring plasmids in <italic>K. pneumoniae</italic>, with <italic>bla</italic><sub>OXA-48</sub>, <italic>bla</italic><sub>OXA-232</sub>, and <italic>bla</italic><sub>OXA-181</sub> being highly prevalent. In <italic>K. pneumoniae</italic>, <italic>bla</italic><sub>OXA-48</sub> was mainly carried by the composite transposon Tn<italic>1999.2</italic> located on IncL/M-type conjugative plasmids, which were mainly geographically distributed in Switzerland, Germany, and China. In <italic>K. pneumoniae</italic>, the <italic>bl</italic>a<sub>OXA-232</sub> gene was mainly carried by 6.1-kb ColKP3-type mobilizable plasmids, which were mainly isolated in India. In <italic>K. pneumoniae</italic>, <italic>bla</italic><sub>OXA-181</sub> 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 <italic>bla</italic><sub>OXA-245</sub>-harboring 65.9-kb IncL plasmids of <italic>K. pneumoniae</italic> isolated in Spain were found to have the genetic context of <italic>bla</italic><sub>OXA-245</sub> more complicated than that of <italic>bla</italic><sub>OXA-48</sub>-harboring IncL/M-type plasmids, with two copies of IS<italic>1R</italic> inserted both upstream and downstream of <italic>bla</italic><sub>OXA-245</sub>-<italic>lysR</italic>. These findings enhance our understanding of the genetic diversity of <italic>bla</italic><sub>OXA-48</sub>-like-harboring plasmids in <italic>K. pneumoniae</italic>.</p>