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Polymyxin acts as an ultimate line of refuge against the severe infections by multidrug-resistant Gram-negative pathogens. This conventional idea is challenged dramatically by the recent discovery of mobile colistin resistance gene (mcr-1) is prevalent in food animals and human beings worldwide. More importantly, the mcr-1 gene was found to be co-localized with other antibiotic resistance genes, raising the possibility that super-bugs with pan-drug resistance are emerging. However, little is reported on the genomes of the mcr-1-positive bacterial host reservoirs. Here we report genome sequencing of three human isolates of the mcr-1-positive Escherichia coli (E15004, E15015 and E15017) and define general features through analyses of bacterial comparative genomics. Fur- ther genomic mining together with sequence typing allowed us to elucidate that the MCR-1-carrying E. coli E15017 belongs to the sequence type ST648 and copro-duces extended-spectrum b-lactamase (ESBL). Given the fact that ST648 has been known to associate with either New Delhi metallo-b-lactamase 1 or ESBL, our results highlighted the possibility of ST648 as an epidemic clone with multidrug resistances.