Genomic Epidemiology of Carbapenemase-producing Klebsiella pneumoniae in China

Cuidan Li; Xiaoyuan Jiang; Tingting Yang; Yingjiao Ju; Zhe Yin; Liya Yue; Guannan Ma; Xuebing Wang; Ying Jing; Xinhua Luo; Shuangshuang Li; Xue Yang; Fei Chen; Dongsheng Zhou

doi:10.1016/j.gpb.2022.02.005

Genomic Epidemiology of Carbapenemase-producing Klebsiella pneumoniae in China

Genomics Proteomics Bioinformatics. 2022 Dec;20(6):1154-1167. doi: 10.1016/j.gpb.2022.02.005. Epub 2022 Mar 18.

Authors

Cuidan Li¹, Xiaoyuan Jiang², Tingting Yang³, Yingjiao Ju³, Zhe Yin⁴, Liya Yue¹, Guannan Ma¹, Xuebing Wang¹, Ying Jing⁴, Xinhua Luo⁴, Shuangshuang Li³, Xue Yang³, Fei Chen⁵, Dongsheng Zhou⁶

Affiliations

¹ CAS Key Laboratory of Genome Sciences & Information, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China.
² CAS Key Laboratory of Genome Sciences & Information, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
³ CAS Key Laboratory of Genome Sciences & Information, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
⁴ State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
⁵ CAS Key Laboratory of Genome Sciences & Information, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Urumqi 830011, China; Beijing Key Laboratory of Genome and Precision Medicine Technologies, Beijing 100101, China. Electronic address: chenfei@big.ac.cn.
⁶ State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China. Electronic address: zhouds@bmi.ac.cn.

Abstract

The rapid spread of carbapenemase-producing Klebsiella pneumoniae (cpKP) poses serious threats to public health; however, the underlying genetic basis for its dissemination is still unknown. We conducted a comprehensive genomic epidemiology analysis on 420 cpKP isolates collected from 70 hospitals in 24 provinces/autonomous regions/municipalities of China during 2009-2017 by short-/long-read sequencing. The results showed that most cpKP isolates were categorized into clonal group 258 (CG258), in which ST11 was the dominant clone. Phylogenetic analysis revealed three major clades including the top one of Clade 3 for CG258 cpKP isolates. Additionally, carbapenemase gene analysis indicated that bla_KPC was dominant in the cpKP isolates, and most bla_KPC genes were located in five major incompatibility (Inc) groups of bla_KPC-harboring plasmids. Importantly, three advantageous combinations of host-bla_KPC-carrying plasmid (Clade 3.1+3.2-IncFII_pHN7A8, Clade 3.1+3.2-IncFII_pHN7A8:IncR, and Clade 3.3-IncFII_pHN7A8:Inc_pA1763-KPC) were identified to confer cpKP isolates the advantages in both genotypes (strong correlation/coevolution) and phenotypes (resistance/growth/competition) to facilitate the nationwide spread of ST11/CG258 cpKP. Intriguingly, Bayesian skyline analysis illustrated that the three advantageous combinations might be directly associated with the strong population expansion during 2007-2008 and subsequent maintenance of the population of ST11/CG258 cpKP after 2008. We then examined drug resistance profiles of these cpKP isolates and proposed combination treatment regimens for CG258/non-CG258 cpKP infections. Thus, the findings of our systematical analysis shed light on the molecular epidemiology and genetic basis for the dissemination of ST11/CG258 cpKP in China, and much emphasis should be given to the close monitoring of advantageous cpKP-plasmid combinations.

Keywords: Carbapenemase; Drug resistance; Genomic epidemiology; Klebsiella pneumoniae; Plasmid.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / pharmacology
Anti-Bacterial Agents / therapeutic use
Bacterial Proteins* / genetics
Bayes Theorem
China / epidemiology
Genomics
Klebsiella pneumoniae* / genetics
Phylogeny
Plasmids / genetics

Substances

carbapenemase
Bacterial Proteins
Anti-Bacterial Agents