Work

IS26 carrying blaKPC−2 mediates carbapenem resistance heterogeneity in extensively drug-resistant Klebsiella pneumoniae isolated from clinical sites

Year: 2025

Type: article

Abstract: Due to the widespread and irrational use of antibiotics, the emergence and prevalence of carbapenem-resistant Klebsiella pneumoniae ( K. pneumoniae ) have become a major challenge in controlling bacterial infections in hospitals. The bla KPC−2 gene located on mobile genetic elements has further complicated the control of resistant bacteria transmission. In this study, K. pneumoniae strains were isolated from blood cultures of patients. Using the Kirby-Bauer disk diffusion method, we found carbapenem resistance heterogeneity. The resistant subpopulation KPTA-R1 and the sensitive subpopulation KPTA-S1 were purified. Whole-genome sequencing revealed that the bla KPC−2 gene in KPTA-R1 was located on an IncFII plasmid (pKPC-R), within a composite transposon (PCTs) formed by two direct repeats of IS 26 elements. The structure was identified as IS 26 - RecA -IS Kpn27 - bla KPC−2 -IS Kpn6 -IS 26 . However, in KPTA-S1, a similar plasmid, pAR-S, lacked this segment. Sequence comparison analysis indicates that the deletion of this bla KPC−2 encoding sequence in this IncFII plasmid is associated with transposition activity mediated by IS 26 . Multi-sequence comparison of the plasmids showed that the IS 26 transposon facilitated the sequence polymorphism of these plasmids. This study reveals the key role of IS 26 -mediated transposition activity, through homologous recombination, in the emergence of carbapenem resistance heterogeneity in clinical K. pneumoniae strains carrying bla KPC−2 . IS 26 is able to promote the evolution of resistance in the IncFII plasmid, and through copy-in cointegration or targeted conservative cointegration may result in the acquisition or loss of antibiotic resistance, which may affect clinical care and pose a public health risk.

Source: Mobile DNA

DOI: 10.1186/s13100-025-00351-2