Molecular epidemiology and genomic insights into Enterobacter cloacae complex co-harbouring bla_KPC and mcr:...

This study aims to systematically investigate the molecular epidemiology and genomic characteristics of Enterobacter cloacae complex (ECC) strains globally harbouring bla_KPC and mcr, as well as the co-existence of drug resistance genes. The goal is to provide insights and recommendations for monitoring clinical drug-resistant strains and super-resistant plasmids.

This study analysed 281 ECC isolates harbouring both bla_KPC and mcr, obtained from NCBI GenBank database (2003-2024) with whole-genome sequencing data. We constructed a phylogenetic tree of ECC strains for phylogenetic analysis. Resistance genes were identified using the ABRicate and CARD databases, and their distribution was examined. Plasmid replicon types for bla_KPC and mcr were analysed with PlasmidFinder, including upstream and downstream genetic environments of these genes.

The predominant genotype combinations harbouring both bla_KPC and mcr are bla_KPC-3 and mcr-9.1, followed by bla_KPC-4 and mcr-9.1, with the dominant strain being E. hormaechei ssp. xiangfangensis. The IncHI2(2A) plasmid co-harbouring bla_KPC and mcr-9 was mainly detected in genomes from the United States. Phylogenetic analysis indicated that the bla_KPC-mcr-9-IncHI2(2A) plasmids in ECC strains have a high genetic similarity to mcr-9-IncHI2(2A), suggesting that the latter may have acquired the additional highly transferable bla_KPC.

ECC strains have become an important reservoir cluster for bla_KPC and mcr-9, and the IncHI2(2A) plasmid is a potential vector for the horizontal co-transmission of carbapenem and colistin resistance genes. Effective monitoring should be implemented to assess the prevalence of co-harbouring bla_KPC and mcr-9 in individual ECC isolates and even in single plasmid.