Genomic characterization of bla IMP -harboring plasmids in Klebsiella spp.

ABSTRACT The spread of carbapenem-resistant Klebsiella spp. poses a significant public health threat, partly due to the acquisition of the bla IMP genes, which encode IMP-type metallo-β-lactamases. These enzymes confer resistance to a broad spectrum of β-lactam antibiotics, including carbapenems, thereby complicating treatment options. This study aims to provide a comprehensive genomic characterization of bla IMP -harboring plasmids across different species within the genus Klebsiella , based on the genomic characteristics of the plasmid pT117-2 of Klebsiella variicola strain T117 isolated from clinical settings in China, along with all available bla IMP -harboring plasmids of Klebsiella spp. fromthe GenBank database until 26 April 2025. Among the 123 bla IMP -harboring plasmids of Klebsiella spp., nine variants were identified, with bla IMP-4 (carried by 69 plasmids) and bla IMP-1 (carried by 37 plasmids) being the most prevalent. The bla IMP-4 gene was associated with IncN type (~50 kb, conjugative) and untypeable (~300 kb, non-mobilizable) plasmids in China, whereas in Australia, it was linked to IncC (~200 kb) and IncM2 (~80 kb) type conjugative plasmids. Meanwhile, bla IMP-1 was found to be associated with IncN (~50 kb), IncM (~80 kb), and IncFII (80 ~200 kb) type conjugative plasmids mainly in Japan. Notably, our results highlight the prevalence of IncN-type conjugative plasmids, including the plasmid pT117-2 identified in this study, as key vehicles for the dissemination of bla IMP genes. This study provides critical insights into the genetic mechanisms of bla IMP -harboring plasmids persistence and spread in Klebsiella spp., advancing our understanding of their dissemination. IMPORTANCE Carbapenem-resistant Enterobacterales (CRE) mediated by metallo-β-lactamases (MBLs) pose a major global public health threat that challenges clinical antimicrobial therapy; based on our study, bla IMP-4 in China is predominantly associated with IncN plasmids (forming the “IncN- bla IMP-4 - qnrS1 ” axis), while bla IMP-1 in Japan links to IncN/IncM/IncFII plasmids, with these regional differences highlighting the need for geographically targeted surveillance, and notably, the high-risk ST146 Klebsiella variicola carrying bla IMP-4 on a conjugative IncN plasmid serves as an underrecognized reservoir for resistance genes, extending surveillance beyond common pathogenic Enterobacterales ; limitations of this study include restricted sample size and geographic scope, and future research should validate these patterns via multi-center studies, explore plasmid evolution mechanisms, and integrate findings into routine surveillance to optimize antibiotic stewardship and infection control, thereby mitigating the global spread of MBL-mediated CRE.