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However, the evolutionary trajectory of the mobile colistin resistome in bacteria is largely unknown. To investigate the coevolution and fitness cost of the colistin resistance genes in wild strains, different assays to uncover the genomic dynamics of <jats:italic>mcr\u20101<\/jats:italic> and <jats:italic>mcr\u20103<\/jats:italic> in bacterial populations are utilized. <jats:italic>Escherichia coli<\/jats:italic> strains harboring both <jats:italic>mcr\u20101<\/jats:italic> and <jats:italic>mcr\u20103.1\/3.5<\/jats:italic> are isolated and <jats:italic>mcr<\/jats:italic> genes are associated with diverse mobile elements. Under exposure to colistin, the <jats:italic>mcr\u20101<\/jats:italic>\u2010bearing resistome is stably inherited during bacterial replication, but <jats:italic>mcr\u20103<\/jats:italic> is prone to be eliminated in populations of certain strains. In the absence of colistin, the persistence rates of the <jats:italic>mcr\u20101<\/jats:italic> and <jats:italic>mcr\u20103<\/jats:italic>\u2010bearing subclones varies depending on the genomic background. The decay of the <jats:italic>mcr<\/jats:italic>\u2010bearing bacterial populations can be mediated by the elimination of <jats:italic>mcr<\/jats:italic>\u2010containing segments, large genomic deletions, and plasmid loss. Mobile elements, including plasmids and transposons, are double\u2010edged swords in the evolution of the resistome. The findings support the idea that antibiotic overuse accounts for global spread of multidrug\u2010resistant (MDR) bacteria. Therefore, stringent regulation of antibiotic prescription for humans and animals should be performed systematically to alleviate the threat of MDR bacteria.<\/jats:p>","DOI":"10.1002\/gch2.202000014","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T07:27:47Z","timestamp":1610695667000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Comprehensive Genomic Investigation of Coevolution of <i>mcr<\/i> genes in <i>Escherichia coli<\/i> Strains via Nanopore Sequencing"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8333-9891","authenticated-orcid":false,"given":"Ruichao","family":"Li","sequence":"first","affiliation":[{"name":"Jiangsu Co\u2010Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses College of Veterinary Medicine Yangzhou University  Yangzhou 225009 P. R. 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