Characterization of a Conjugative Hybrid Plasmid Coharboring bla KPC-2 and bla IMP-4 in a Klebsiella quasipneumoniae Clinical Isolate

Abstract

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. Generation of hybrid MDR plasmids accelerated the evolution and transmission of resistance genes. In this study, we characterized a bla KPC-2 - and bla IMP-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 bla IMP-4 gene was captured by a novel integron In 1965 , and the bla KPC-2 gene was located on a new non-Tn 4401 group I NTE KPC element. Both bla KPC-2 - and bla IMP-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.