Genomic Characterization of an Extensively Drug-Resistant Klebsiella pneumoniae Co-harboring mcr-3.11, blaNDM-5 and blaCTX-M-27 isolated from Pelvic Effusion in a Colon Cancer Patient

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Abstract

Objective The global dissemination of carbapenem-resistant Klebsiella pneumoniae (CRKP), particularly strains co-harboring plasmid-mediated colistin resistance genes, poses a severe threat to public health. This study aimed to characterize the genomic features and transmission mechanisms of an extensively drug-resistant (XDR) K. pneumoniae (KP2024), which was isolated from the pelvic effusion of a postoperative colon cancer patient and co-harbored the rare mcr-3.11 gene alongside blaNDM-5 and blaCTX-M-27. Results K. pneumoniae KP2024 exhibited an XDR phenotype, Analysis of key resistance mechanisms identified three epidemiologically important plasmids: an IncFIB plasmid carrying blaCTX-M-27 (pKP2024-1), an IncFII plasmid carrying mcr-3.11 (pKP2024-3), and an IncX3 plasmid carrying blaNDM-5 (pKP2024-4). Comparative genomic analysis indicated that blaCTX-M-27 was located within a highly conserved transposition unit mediated by ISEcp1, mcr-3.11 and dgkA form a conserved mobile genetic element, embedded in highly active transposable elements, and blaNDM-5 was located within a typical Tn3-IS3000-IS5- blaNDM-5 - bleMBL - trpF -IS26-ISKox3 structure on IncX3 plasmid. All these plasmidsharbored complete conjugative transfer systems or mobile genetic elements, possessing a high potential for horizontal gene transfer. Conclusion This study is the first to report an XDR K.pneumoniae co-harboring mcr-3.11 , blaNDM-5 , and blaCTX-M-27 , isolated from the postoperative pelvic effusion of a colon cancer patient. Multiple key resistance genes are distributed on different types of mobile plasmids, conferring resistance to “last-line” clinical agents such as carbapenems and colistin. The co-existence of multiple plasmids and the co-evolution of resistance genes amplify the risk of resistance transmission, highlighting the urgent need for enhanced clinical surveillance of such highly resistant clones.

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