Heterogeneous and Flexible Transmission of in Hospital-Associated Escherichia coli.

The recent emergence of a transferable colistin resistance mechanism, MCR-1, has gained global attention because of its threat to clinical treatment of infections caused by multidrug-resistant Gram-negative bacteria. However, the possible transmission route of among species in clinical settings is largely unknown. Here, we present a comprehensive genomic analysis of isolates collected in a hospital in Hangzhou, China. We found that -carrying isolates from clinical infections and feces of inpatients and healthy volunteers were genetically diverse and were not closely related phylogenetically, suggesting that clonal expansion is not involved in the spread of The gene was found on either chromosomes or plasmids, but in most of the isolates, was carried on plasmids. The genetic context of the plasmids showed considerable diversity as evidenced by the different functional insertion sequence (IS) elements, toxin-antitoxin (TA) systems, heavy metal resistance determinants, and Rep proteins of broad-host-range plasmids. Additionally, the genomic analysis revealed nosocomial transmission of and the coexistence of with other genes encoding β-lactamases and fluoroquinolone resistance in the isolates. These findings indicate that is heterogeneously disseminated in both commensal and pathogenic strains of , suggest the high flexibility of this gene in its association with diverse genetic backgrounds of the hosts, and provide new insights into the genome epidemiology of among hospital-associated strains. Colistin represents one of the very few available drugs for treating infections caused by extensively multidrug-resistant Gram-negative bacteria. The recently emergent colistin resistance gene threatens the clinical utility of colistin and has gained global attention. How spreads in hospital settings remains unknown and was investigated by whole-genome sequencing of -carrying in this study. The findings revealed extraordinary flexibility of in its spread among genetically diverse hosts and plasmids, nosocomial transmission of -carrying , and the continuous emergence of novel Inc types of plasmids carrying and new variants. Additionally, was found to be frequently associated with other genes encoding β-lactams and fluoroquinolone resistance. These findings provide important information on the transmission and epidemiology of and are of significant public health importance as the information is expected to facilitate the control of this significant antibiotic resistance threat.