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

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.

Emergence of the Coexistence of mcr-1, blaNDM-5, and blaCTX-M-55 in Klebsiella pneumoniae ST485 Clinical Isolates in China

“…Sequencing analysis showed that in addition to the bla KPC-2 gene, one or more other kinds of β-lactamase genes (such as bla CTX-M , bla SHV , and bla TEM ) were identified in these KPC-producing K. pneumoniae strains, with 53% (8/15) of the strains carrying the ESBL gene, bla CTX-M ; this is consistent with previous reports. 23 Consistent with other studies, the isolates were also more resistant to quinolones and trimethoprim/sulfamethoxazole. Quite often, plasmids carrying ESBL genes also carry other drug-resistant genes including quinolone and trimethoprim/sulfamethoxazole resistance genes.…”

Convergence of MCR-8.2 and Chromosome-Mediated Resistance to Colistin and Tigecycline in an NDM-5-Producing ST656 Klebsiella pneumoniae Isolate From a Lung Transplant Patient in China

“…MLST analysis showed that the K. pneumoniae strain KP32558 was assigned to ST656, a rare ST type and firstly reported in China in 2012 ( Wang et al., 2012 ). The frequently detected carbapenemase in these bacteria was KPC-2 ( Liu et al., 2021 ) and NDM-1 ( Li et al., 2020 ). Our study represents the first report of the emergence of NDM-5 and MCR in ST656 K. pneumoniae clinical isolate.…”

An Outbreak of Carbapenem-Resistant Klebsiella pneumoniae in an Intensive Care Unit of a Major Teaching Hospital in Chongqing, China

“…The acquisition of conjugant resistance also showed that drug resistance was transferable. bla TEM is often part of the genetic environment of bla KPC-2 ( Liu et al., 2021 ; Zhai et al., 2021 ), so both genes were transferred within the plasmid. In Europe and the United States, transposon Tn 4401 is the most common gene element carrying bla KPC ( Naas et al., 2008 ; Wang et al., 2015 ).…”