Genomic characterisation of a multidrug-resistant Klebsiella pneumoniae co-harbouring blaNDM-1, blaKPC-2, and tet(A) isolated from the bloodstream infections of patients

Objectives: Carbapenem-resistant Klebsiella pneumoniae (CRKP), a superbug that can be difficult or impossible to treat, has become a worldwide problem. This study presents the first report of a CRKP strain carrying a plasmid co-harbouring blaNDM-1 , blaKPC-2 , and tet(A) and the subsequent analysis of its genomic features. Methods: Isolation and identification of bacteria, antimicrobial susceptibility test, whole genome sequencing, and conjugation experiments assay were conducted in clinical epidemiological investigations and plasmid genetic characterisation analysis. Results: A total of 116 strains of bacteria were isolated from patients with bloodstream infections (BSI) between 2018 and 2023. A total of 89.66% of the isolates were carbapenem-resistant Enterobacteriaceae (CRE), with the majority (75/116) being CRKP. Among these, a novel plasmid co-harbouring blaNDM-1 , blaKPC-2 , and tet(A) simultaneously was found in CRKP46, and the three genes mediated conjugation by IS 26 , IS Aba125 , and IS 26 , respectively. This plasmid conferred carbapenem resistance to E. coli J53 after conjugative transfer, which was 2 times greater than that of CRKP46. Conclusion: The present study identified the occurrence of a rare plasmid co-harbouring blaNDM-1 , blaKPC-2 , and tet(A) , and the spread of these genes was mediated by the corresponding mobile elements. The increased carbapenem resistance created by this novel plasmid challenges public health security and poses a potential threat to human health; therefore, it deserves attention. (c) 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights are reserved, including those for text and data mining, AI training, and similar technologies.