Global genomic and molecular epidemiology of carbapenem-resistant Enterobacter hormaechei

Carbapenem-resistant Enterobacter hormaechei (CR-Eh) represents a critical global health threat, especially when carrying mobile antimicrobial resistance genes (ARGs) like bla_NDM and mcr. This study characterized three clinical CR-Eh isolates in the context of global genomic datasets, identifying distinct patterns of resistance gene carriage. Notably, bla_NDM-1 was found duplicated on the chromosome of strain BC18 but resided on plasmids in other isolates. In contrast, mcr-9 was detected in a conserved genetic context on an IncHI2 plasmid. Analysis of publicly available genomes from 47 countries demonstrated that bla_NDM variants (primarily bla_NDM-1 and bla_NDM-5) and mcr-9 are widely distributed globally. Within the available dataset, the isolates exhibited high genetic diversity, with numerous sequence types (including high-risk clones ST171 and ST190) and plasmids (IncX3/IncHI2) implicated in their spread. The strains carried an average of 14 ARGs each, and phylogenetic analysis suggested potential for cross-border and cross-habitat transmission. Collectively, our findings underscore that E. hormaechei is not merely a pathogen but a highly adaptable genetic reservoir for ARG accumulation and dissemination, highlighting the urgent need for systematic One Health genomic surveillance.