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

• Main Authors: Liu H, Lin H, Sun Z, Zhu X, Zhang X, Li Q, Lu J, Lin X, Lin L, Li K, Zhu M, Bao Q, Xu T, Hu Y, Zhang H
• Format: Article
• Language: English
• Published: Dove Medical Press 2021-01-01
• Series: Infection and Drug Resistance
• Subjects: carbapenemase; crkp; blakpc-2; kpc-kp; st11; tn1721
• Online Access: https://www.dovepress.com/distribution-of-beta-lactamase-genes-and-genetic-context-of-blakpc-2-i-peer-reviewed-article-IDR

Hongmao Liu,1– 3,* Hailong Lin,1– 3,* Zhewei Sun,2,3 Xinyi Zhu,1– 3 Xueya Zhang,1– 3 Qiaoling Li,1– 3 Junwan Lu,2,3 Xi Lin,2,3 Li Lin,1,3 Kewei Li,2,3 Mei Zhu,4 Qiyu Bao,2,3 Teng Xu,5 Yunliang Hu,1– 3 Hailin Zhang1,3 1The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou 325027, People’s Republic of China; 2Key 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; 3Institute of Biomedical Informatics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, People’s Republic of China; 4Department of Clinical Laboratory, Zhejiang Hospital, Hangzhou, Zhejiang 310013, People’s Republic of China; 5Institute of Translational Medicine, Baotou Central Hospital, Baotou 014040, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yunliang Hu; Hailin ZhangThe Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou 325027, People’s Republic of ChinaTel/Fax [phone]; Tel [phone]Email [e-mail]; [e-mail]: 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 blaKPC-2 gene. Conjugation experiments were performed to evaluate the transferability of blaKPC-2-bearing plasmids. Multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were performed to investigate the clonal relatedness of blaKPC-2-producing strains.Results: The blaKPC-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 blaKPC-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 blaKPC-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 blaKPC-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: carbapenemase, CRKP, blaKPC-2, KPC-Kp, ST11, Tn 1721