Molecular characterization and comparison of bla NDM-1-carrying and bla NDM-5-harboring IncX3-type plasmids in carbapenem-resistant Klebsiella pneumoniae

Yunxing Yang; Haiyang Liu; Lingxia Chen; Minjie Mao; Xiaofan Zhang; Longjie Zhou; Darong Duan; Xi Li; Hua Zhou

doi:10.1128/spectrum.01028-23

Molecular characterization and comparison of bla _NDM-1-carrying and bla _NDM-5-harboring IncX3-type plasmids in carbapenem-resistant Klebsiella pneumoniae

Microbiol Spectr. 2023 Aug 25;11(5):e0102823. doi: 10.1128/spectrum.01028-23. Online ahead of print.

Authors

Yunxing Yang^#¹, Haiyang Liu^#², Lingxia Chen^#², Minjie Mao³, Xiaofan Zhang², Longjie Zhou², Darong Duan⁴, Xi Li², Hua Zhou⁵

Affiliations

¹ Department of Clinical Laboratory, Affiliated Hangzhou First People's Hospital, Zhejiang School of Medicine , Hangzhou, China.
² Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College) , Hangzhou, Zhejiang, China.
³ Department of Clinical Laboratory, The First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University , Jiaxing, Zhejiang, China.
⁴ Department of Laboratory Medicine, Huangyan Hospital of Wenzhou Medical University, Taizhou First People' s Hospital , Taizhou, Zhejiang, China.
⁵ Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang, China.

^# Contributed equally.

Abstract

Carbapenem-resistant Klebsiella pneumoniae (CRKP), which harbors the bla _NDM plasmid, has been reported extensively and is considered a global threat clinically. However, characterization and comparisons of bla _NDM-1-carrying and bla _NDM-5-harboring IncX3-type plasmids in CRKP are lacking. Here, we systematically compared the differences in the characteristics, genetic backgrounds, transferability, and fitness costs between bla _NDM-1-carrying and bla _NDM-5-carrying plasmids in K. pneumoniae isolates. Fifteen NDM-producing CRKP isolates were recovered from 1376 CRKP isolates between 2019 and 2021, of which 4 were positive for bla _NDM-1 and 11 were positive for bla _NDM-5. All strains were highly resistant to carbapenem but remained susceptible to tigecycline and colistin. Core-genome-based phylogenetic analyses revealed that these strains were not clonally related. Whole-genome sequencing showed that bla _NDM-1 and bla _NDM-5 were located on ~54 kb and ~46 kb IncX3-type plasmids, respectively. The backbone, genetic context, and fitness cost of the bla _NDM-1-bearing plasmid were highly similar to those of the bla _NDM-5-carrying plasmid, but the transferability of the bla _NDM-1-positive plasmid was greater than that of the bla _NDM-5-positive plasmid. In conclusion, the transmission of bla _NDM-1 or bla _NDM-5 is mainly disseminated by plasmids rather than clonal spread. The high transfer frequency of the IncX3 plasmid facilitates the prevalence and dissemination of NDM-KP among Enterobacteriaceae. IMPORTANCE The emergence of NDM-producing Klebsiella pneumoniae is a severe challenge to public health. The widespread presence of bla _NDM-1 and bla _NDM-5 in Enterobacteriaceae has aroused broad concern. In this study, we performed molecular characterization of bla _NDM-1-carrying and bla _NDM-5-harboring IncX3-type plasmids in carbapenem-resistant Klebsiella pneumoniae (CRKP) and compared their phenotypes between strains with different bla _NDM subtype. Our findings highlight the importance of IncX3-type plasmids in the transfer of the bla _NDM-1 and bla _NDM-5 genes and demonstrate that the bla _NDM-1 plasmid possesses higher transfer ability. These data will provide important insights into carbapenem resistance gene transfer via plasmids and their further spread in clinical settings.

Keywords: IncX3; NDM-1; NDM-5; carbapenemases; fitness.