Genomic characterization of Enterobacter isolates highlights widespread ST78 high-risk clone and plasmid-mediated dissemination of bla NDM-1

Species of the genus Enterobacter are considered priority pathogens due to their extensive antimicrobial resistance, primarily driven by transmissible β-lactamases. We conducted whole-genome sequencing of clinical isolates of Enterobacter spp. collected between 2020 and 2024 across 14 federal entities in Mexico. Subspecies-level identification revealed the predominance of Enterobacter hormaechei subsp. steigerwaltii and E. hormaechei subsp. xiangfangensis , the latter showing the highest resistance rates to tested antimicrobial agents. Resistome profiling identified bla NDM-1 as the most prevalent carbapenemase among carbapenem-resistant isolates. Mobilome analysis showed that bla NDM-1 was predominantly carried by plasmids of the IncFIB/IncFII/rep_cluster_2272 type. Phylogenomic comparisons with public genomes, combined with the dominance of bla NDM-1 , suggest transcontinental dissemination. Notably, international clones of E. hormaechei subspecies, such as ST182 and ST78, were identified, alongside regionally relevant clones such as ST92, ST45, ST116, and ST93. Finally, genomic evidence supports the existence of a putative novel Enterobacter species related to Enterobacter bugandensis , Enterobacter nematophilus , and Enterobacter chuandaensis . IMPORTANCE Enterobacter species pose a global threat due to their capacity to acquire and disseminate antimicrobial resistance. Currently, there is no genomic surveillance data from Mexico, limiting the understanding of the national molecular epidemiology and its connection with global trends. This study provides the first nationwide genomic overview of Enterobacter in Mexico. Our findings highlight the detection of both localized and widespread clones, including a recognized high-risk lineage, and dissemination of bla NDM . Beyond public health implications, we describe a putative novel species. By making this genomic data publicly available, this work contributes to the generation of data needed for surveillance, outbreak detection, and strategies to control antimicrobial resistance in Enterobacter species.