Distribution of β-Lactamase Genes and Genetic Context of bla KPC-2 in Clinical Carbapenemase-Producing Klebsiella pneumoniae Isolates

Hongmao Liu; Hailong Lin; Zhewei Sun; Xinyi Zhu; Xueya Zhang; Qiaoling Li; Junwan Lu; Xi Lin; Li Lin; Kewei Li; Mei Zhu; Qiyu Bao; Teng Xu; Yunliang Hu; Hailin Zhang

doi:10.2147/IDR.S290434

Distribution of β-Lactamase Genes and Genetic Context of bla _KPC-2 in Clinical Carbapenemase-Producing Klebsiella pneumoniae Isolates

Infect Drug Resist. 2021 Jan 26:14:237-247. doi: 10.2147/IDR.S290434. eCollection 2021.

Authors

Hongmao Liu^#^{1

2

3}, Hailong Lin^#^{1

2

3}, Zhewei Sun^{2

3}, Xinyi Zhu^{1

2

3}, Xueya Zhang^{1

2

3}, Qiaoling Li^{1

2

3}, Junwan Lu^{2

3}, Xi Lin^{2

3}, Li Lin^{1

3}, Kewei Li^{2

3}, Mei Zhu⁴, Qiyu Bao^{2

3}, Teng Xu⁵, Yunliang Hu^{1

2

3}, Hailin Zhang^{1

3}

Affiliations

¹ The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou 325027, People's Republic of China.
² Key Laboratory of Medical Genetics of Zhejiang Province, Key Laboratory of Laboratory Medicine, Ministry of Education, China, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, People's Republic of China.
³ Institute of Biomedical Informatics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, People's Republic of China.
⁴ Department of Clinical Laboratory, Zhejiang Hospital, Hangzhou, Zhejiang 310013, People's Republic of China.
⁵ Institute of Translational Medicine, Baotou Central Hospital, Baotou 014040, People's Republic of China.

^# Contributed equally.

Abstract

Background: This study was designed to characterize the dissemination mechanism and genetic context of Klebsiella pneumoniae carbapenemase (KPC) genes in carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates.

Methods: A retrospective analysis was performed on CRKP strains isolated from a teaching hospital of Wenzhou Medical University during 2015-2017. Polymerase chain reaction (PCR)-based amplification and whole-genome sequencing (WGS) were used to analyze the genetic context of the bla _KPC-2 gene. Conjugation experiments were performed to evaluate the transferability of bla _KPC-2-bearing plasmids. Multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were performed to investigate the clonal relatedness of bla _KPC-2-producing strains.

Results: The bla _KPC-2 gene was identified from 13.61% (40/294) of clinical K. pneumoniae isolates. Three different sequence types (ST11, ST15 and ST656) and 5 PFGE subtypes (A to E) were classified among them. ST11 was the dominant sequence type (92.50%, 37/40). Plasmid-oriented antibiotic resistance genes, such as extended spectrum-β-lactamases (ESBLs) and other antimicrobial resistance genes, were also found in KPC-positive K. pneumoniae (KPC-Kp) isolates. Mapping PCR and genomic sequencing revealed that the bla _KPC-2-bearing sequence regions, which are related to different mobile elements, including Tn1721- and IS26-based transposons, were mainly located in but not restricted to IncFII-like plasmids and were structurally divergent.

Conclusion: The bla _KPC-2 genes related to divergent mobile genetic elements encoded on transferable plasmids may transfer widely, facilitating the spread of carbapenem resistance among bacteria with different genetic backgrounds. The dissemination of bla _KPC-bearing plasmids that collectively carry additional multidrug resistance genes has caused widespread public concern, further limiting the antibiotics available to treat infections caused by KPC-producing pathogens.

Keywords: CRKP; KPC-Kp; ST11; Tn1721; blaKPC-2; carbapenemase.

Grants and funding

This study was supported by the National Natural Science Foundation of China (81973382, 81960381 and 81700011); the Natural Science Foundation of Zhejiang Province, China (LY19C060002, LQ17H190001 and LQ17H010003); the Special Project for Significant New Drug Research and Development in the Major National Science and Technology Projects of China (2020ZX09201002); the Science & Technology Project of Wenzhou City, China (Y2020112, Y20170205 and 2019Y0358) and the Science & Technology Project of Inner Mongolia Autonomous Region, China (201802125).