AUTHOR=Zeng Zhu , Lei Lei , Li Linman , Hua Shengni , Li Wenting , Zhang Limei , Lin Qiuping , Zheng Zhixiong , Yang Jing , Dou Xiaohui , Li Luan , Li Xiaobin 

TITLE=In silico characterization of blaNDM-harboring plasmids in Klebsiella pneumoniae

JOURNAL=Frontiers in Microbiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.1008905

DOI=10.3389/fmicb.2022.1008905

ISSN=1664-302X

ABSTRACT=<p><italic>Klebsiella pneumoniae</italic> is a primary culprit of antibiotic-resistant nosocomial infections worldwide, and infections caused by NDM-producing strains are a major threat due to limited therapeutic options. The majority of <italic>bla</italic><sub>NDM</sub> cases occur on plasmids; therefore, we explored the relationships between plasmids and <italic>bla</italic><sub>NDM</sub> genes in <italic>K. pneumoniae</italic> by analyzing the variants of <italic>bla</italic><sub>NDM</sub>, replicon types, conjugative transfer regions of 171 <italic>bla</italic><sub>NDM</sub>-harboring plasmids from 4,451 <italic>K. pneumoniae</italic> plasmids. Of the nine identified <italic>bla</italic><sub>NDM</sub> variants, <italic>bla</italic><sub>NDM-1</sub> (73.68%) and <italic>bla</italic><sub>NDM-5</sub> (16.37%) were the most dominant. Over half of the <italic>bla</italic><sub>NDM</sub>-harboring plasmids of <italic>K. pneumoniae</italic> were classified into IncF plasmids. IncX3 single-replicon plasmids (46–57 kb) carried genes encoding relaxases of the MOB<sub>P</sub> family, T4CP genes of the VirD4/TraG subfamily, and VirB-like T4SS gene clusters, which were mainly geographically distributed in China. We found 10 <italic>bla</italic><sub>NDM</sub>-harboring IncN plasmids (38.38–63.05 kb) carrying the NW-type origin of transfer (<italic>oriT</italic>) regions, genes coding for relaxases of MOB<sub>F</sub> family, genes encoding T4CPs of the TrwB/TraD subfamily, and Trw-like T4SS gene clusters, which were also mainly geographically distributed in China. Moreover, we identified 21 IncC plasmids carrying <italic>bla</italic><sub>NDM-1</sub> (140.1–329.2 kb), containing the A/C-type <italic>oriT</italic>s, genes encoding relaxases of MOB<sub>H</sub> family, genes encoding T4CPs belonging to TrwB/TraD subfamily, and Tra_F-like T4SS gene clusters. The <italic>bla</italic><sub>NDM</sub>-harboring IncC plasmids were widely geographically distributed all over the world, mainly in the United States, China and Viet Nam. These findings enhance our understanding of the diversity of <italic>bla</italic><sub>NDM</sub>-harboring plasmids in <italic>K. pneumoniae</italic>.</p>