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However, the possible transmission route of\n            <jats:italic>mcr-1<\/jats:italic>\n            among\n            <jats:italic>Enterobacteriaceae<\/jats:italic>\n            species in clinical settings is largely unknown. Here, we present a comprehensive genomic analysis of\n            <jats:named-content content-type=\"genus-species\">Escherichia coli<\/jats:named-content>\n            isolates collected in a hospital in Hangzhou, China. We found that\n            <jats:italic>mcr-1<\/jats:italic>\n            -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\n            <jats:italic>mcr-1<\/jats:italic>\n            . The\n            <jats:italic>mcr-1<\/jats:italic>\n            gene was found on either chromosomes or plasmids, but in most of the\n            <jats:named-content content-type=\"genus-species\">E.\u00a0coli<\/jats:named-content>\n            isolates,\n            <jats:italic>mcr-1<\/jats:italic>\n            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\n            <jats:italic>mcr-1<\/jats:italic>\n            and the coexistence of\n            <jats:italic>mcr-1<\/jats:italic>\n            with other genes encoding \u03b2-lactamases and fluoroquinolone resistance in the\n            <jats:named-content content-type=\"genus-species\">E.\u00a0coli<\/jats:named-content>\n            isolates. These findings indicate that\n            <jats:italic>mcr-1<\/jats:italic>\n            is heterogeneously disseminated in both commensal and pathogenic strains of\n            <jats:named-content content-type=\"genus-species\">E.\u00a0coli<\/jats:named-content>\n            , 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\n            <jats:italic>mcr-1<\/jats:italic>\n            among hospital-associated\n            <jats:named-content content-type=\"genus-species\">E.\u00a0coli<\/jats:named-content>\n            strains.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Colistin represents one of the very few available drugs for treating infections caused by extensively multidrug-resistant Gram-negative bacteria. The recently emergent\n            <jats:italic>mcr-1<\/jats:italic>\n            colistin resistance gene threatens the clinical utility of colistin and has gained global attention. How\n            <jats:italic>mcr-1<\/jats:italic>\n            spreads in hospital settings remains unknown and was investigated by whole-genome sequencing of\n            <jats:italic>mcr-1<\/jats:italic>\n            -carrying\n            <jats:named-content content-type=\"genus-species\">Escherichia coli<\/jats:named-content>\n            in this study. The findings revealed extraordinary flexibility of\n            <jats:italic>mcr-1<\/jats:italic>\n            in its spread among genetically diverse\n            <jats:named-content content-type=\"genus-species\">E.\u00a0coli<\/jats:named-content>\n            hosts and plasmids, nosocomial transmission of\n            <jats:italic>mcr-1<\/jats:italic>\n            -carrying\n            <jats:named-content content-type=\"genus-species\">E.\u00a0coli<\/jats:named-content>\n            , and the continuous emergence of novel Inc types of plasmids carrying\n            <jats:italic>mcr-1<\/jats:italic>\n            and new\n            <jats:italic>mcr-1<\/jats:italic>\n            variants. Additionally,\n            <jats:italic>mcr-1<\/jats:italic>\n            was found to be frequently associated with other genes encoding \u03b2-lactams and fluoroquinolone resistance. These findings provide important information on the transmission and epidemiology of\n            <jats:italic>mcr-1<\/jats:italic>\n            and are of significant public health importance as the information is expected to facilitate the control of this significant antibiotic resistance threat.\n          <\/jats:p>","DOI":"10.1128\/mbio.00943-18","type":"journal-article","created":{"date-parts":[[2018,7,9]],"date-time":"2018-07-09T10:44:50Z","timestamp":1531133090000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":57,"title":["Heterogeneous and Flexible Transmission of\n            <i>mcr-1<\/i>\n            in Hospital-Associated Escherichia coli"],"prefix":"10.1128","volume":"9","author":[{"given":"Yingbo","family":"Shen","sequence":"first","affiliation":[{"name":"Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing, 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Zhejiang University, Hangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong-Wei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Second Affiliated Hospital of Zhejiang University, Zhejiang University, Hangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0866-4584","authenticated-orcid":false,"given":"Shaolin","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Lei","sequence":"additional","affiliation":[{"name":"Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing, 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Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guo-Bao","family":"Tian","sequence":"additional","affiliation":[{"name":"Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Congming","family":"Wu","sequence":"additional","affiliation":[{"name":"Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing, China"},{"name":"Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety and Beijing Laboratory for Food Quality and Safety, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qijing","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Iowa State University, Ames, Iowa, 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