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Although several key plasmid elements that balance\n                    <jats:italic>mcr\u20101<\/jats:italic>\n                    persistence and bacterial growth are identified, the regulatory interactions between\n                    <jats:italic>mcr\u20101<\/jats:italic>\n                    and host bacteria remain poorly understood. Using a genome\u2010wide CRISPRi crRNA library, it is identified that DNA polymerase IV,\n                    <jats:italic>dinB<\/jats:italic>\n                    , is essential for controlling the fitness cost associated with\n                    <jats:italic>mcr\u20101<\/jats:italic>\n                    in\u00a0\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    . The absence of\n                    <jats:italic>dinB<\/jats:italic>\n                    operon enhances\n                    <jats:italic>mcr\u20101<\/jats:italic>\n                    \u2010mediated colistin resistance but simultaneously compromises bacterial growth and competitiveness. Meanwhile,\n                    <jats:italic>dinB<\/jats:italic>\n                    deficiency mitigates inflammatory response in RAW267.4 cells and enhances bacterial colonization in murine tissues. Further investigation reveals that\n                    <jats:italic>mcr\u20101<\/jats:italic>\n                    actively upregulates\n                    <jats:italic>dinB<\/jats:italic>\n                    expression, with the increased reactive oxygen species induced by\n                    <jats:italic>mcr\u20101<\/jats:italic>\n                    being crucial for this activation. \u00a0 These findings suggest that\n                    <jats:italic>dinB<\/jats:italic>\n                    modulates\n                    <jats:italic>mcr<\/jats:italic>\n                    expression and bacterial fitness via a negative feedback regulatory mechanism. Leveraging this regulatory relationship, a Toxin\u2010Intein is engineered under the control of\n                    <jats:italic>dinB<\/jats:italic>\n                    promoter to selectively target and kill\n                    <jats:italic>mcr<\/jats:italic>\n                    \u2010positive\n                    <jats:italic>E. coli<\/jats:italic>\n                    both in vitro and in vivo. Overall, the work uncovers a novel adaptive mechanism underlying\n                    <jats:italic>mcr<\/jats:italic>\n                    persistence and provides a precise antimicrobial strategy to combat antibiotic\u2010resistant pathogens.\n                  <\/jats:p>","DOI":"10.1002\/advs.202411994","type":"journal-article","created":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T06:17:56Z","timestamp":1738304276000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["DNA Polymerase IV\n                    <i>dinB<\/i>\n                    Favors the Adaptive Fitness of\n                    <i>mcr<\/i>\n                    \u2010carrying Bacteria Through a Negative Feedback Regulatory Mechanism"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3473-0186","authenticated-orcid":false,"given":"Haijie","family":"Zhang","sequence":"first","affiliation":[{"name":"Jiangsu 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