Characterization of a Conjugative Hybrid Plasmid Coharboring blaKPC-2 and blaIMP-4 in a Klebsiella quasipneumoniae Clinical Isolate

Abstract

ABSTRACT Generation of hybrid MDR plasmids accelerated the evolution and transmission of resistance genes. In this study, we characterized a blaKPC-2- and blaIMP-4-coharboring conjugative hybrid plasmid constituted of an IncHI5 plasmid-like region, an IncFII(Yp)/IncFIA plasmid-like region, and a KPN1344 chromosome-like region from a clinical ST852-KL18 Klebsiella quasipneumoniae strain. The blaIMP-4 gene was captured by a novel integron In1965, and the blaKPC-2 gene was located on a new non-Tn4401 group I NTEKPC element. Both blaKPC-2- and blaIMP-4-containing genetic architectures were distinguished from classical structures, highlighting the constant evolution of these genetic elements. IMPORTANCE The emergence of carbapenem-resistant Enterobacterales (CRE) that coexpress serine- and metallo-carbapenemases is a severe threat to the efficacy of ceftazidime-avibactam (CZA), which has been proven to be extremely effective against KPC-producing Enterobacterales strains. Our study described the cooccurrence of KPC-2, a serine β-lactamase, and IMP-4, a metallo-β-lactamase (MBL), on a conjugative hybrid plasmid from a clinical carbapenem-resistant K. quasipneumoniae strain, and it revealed an alternative route for IncHI5 plasmid to evolve by recombining with other plasmids to form a hybrid plasmid. Moreover, this hybrid plasmid can be transferred into other Klebsiella species and stably persist during passage. The propagation of two important carbapenemase genes with a new genetic background using well-evolved plasmids in the clinical setting promotes the emergence of superbugs that require careful monitoring.

Keywords

• K. quasipneumoniae
• blaKPC-2
• blaIMP-4
• hybrid plasmid
• IncHI5 plasmid