AUTHOR=Zhang Zhiren , Guo Hengzhao , Li Xiaodong , Li Wenting , Yang Guang , Ni Wenjun , Zhan Meixiao , Lu Ligong , Zhang Zhenlin , Li Xiaobin , Zhou Zhiling 

TITLE=Genetic Diversity and Characteristics of blaNDM-Positive Plasmids in Escherichia coli

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.729952

DOI=10.3389/fmicb.2021.729952

ISSN=1664-302X

ABSTRACT=<p>New Delhi metallo-β-lactamases (NDMs), including at least 28 variants, are a rapidly emerging family of β-lactamases worldwide, with a variety of infections caused by NDM-positive strains usually associated with very poor prognosis and high mortality. NDMs are the most prevalent carbapenemases in <italic>Escherichia coli</italic> (<italic>E. coli</italic>) worldwide, especially in China. The vast majority of <italic>bla</italic><sub>NDM</sub> cases occur on plasmids, which play a vital role in the dissemination of <italic>bla</italic><sub>NDM</sub>. To systematically explore the relationships between plasmids and <italic>bla</italic><sub>NDM</sub> genes in <italic>E. coli</italic> and obtain an overall picture of the conjugative and mobilizable <italic>bla</italic><sub>NDM</sub>-positive plasmids, we analyzed the variants of <italic>bla</italic><sub>NDM</sub>, replicon types, phylogenetic patterns, conjugative transfer modules, host STs, and geographical distributions of 114 <italic>bla</italic><sub>NDM</sub>-positive plasmids, which were selected from 3786 plasmids from 1346 complete whole genomes of <italic>E. coli</italic> from the GenBank database. We also established links among the characteristics of <italic>bla</italic><sub>NDM</sub>-positive plasmids in <italic>E. coli</italic>. Eight variants of <italic>bla</italic><sub>NDM</sub> were found among the 114 <italic>bla</italic><sub>NDM</sub>-positive plasmids, with <italic>bla</italic><sub>NDM</sub><sub>–</sub><sub>5</sub> (74 <italic>bla</italic><sub>NDM</sub><sub>–</sub><sub>5</sub> genes in 73 plasmids), and <italic>bla</italic><sub>NDM</sub><sub>–</sub><sub>1</sub> (31 <italic>bla</italic><sub>NDM</sub><sub>–</sub><sub>1</sub> genes in 28 plasmids) being the most dominant. The variant <italic>bla</italic><sub>NDM</sub><sub>–</sub><sub>5</sub> was mainly carried by the IncX3 plasmids and IncF plasmids in <italic>E. coli</italic>, the former were mainly geographically distributed in East Asia (especially in China) and the United States, and the latter were widely distributed worldwide. IncC plasmids were observed to be the predominant carriers of <italic>bla</italic><sub>NDM</sub><sub>–</sub><sub>1</sub> genes in <italic>E. coli</italic>, which were mainly geographically distributed in the United States and China. Other <italic>bla</italic><sub>NDM</sub><sub>–</sub><sub>1</sub>-carrying plasmids also included IncM2, IncN2, and IncHI1. Moreover, the overall picture of the conjugative and mobilizable <italic>bla</italic><sub>NDM</sub>-positive plasmids in <italic>E. coli</italic> was described in our study. Our findings enhance our understanding of the genetic diversity and characteristics of <italic>bla</italic><sub>NDM</sub>-positive plasmids in in <italic>E. coli</italic>.</p>