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We showed that potential trimethoprim-resistance dihydrofolate reductase (\n            <jats:italic toggle=\"yes\">dfrA<\/jats:italic>\n            ) genes enriched in lytic phages could confer trimethoprim resistance to\n            <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n            . Sequence analysis revealed that lytic phages rarely transfer these potential\n            <jats:italic toggle=\"yes\">dfrA<\/jats:italic>\n            genes into their bacterial hosts. Functional studies showed that these\n            <jats:italic toggle=\"yes\">dfrA<\/jats:italic>\n            genes not only enhance phage reproduction in the presence of trimethoprim but also promote bacterial growth during phage infection. These results highlight that abundant functional ARGs were selected in evolution to improve lytic phage reproduction by promoting bacterial growth during infection, suggesting that\n            <jats:italic toggle=\"yes\">dfrA<\/jats:italic>\n            genes play important roles in evolutionary mutualism between lytic phages and their hosts.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adt4817","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T17:58:32Z","timestamp":1758909512000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":9,"title":["Evolutionary selection of trimethoprim-resistant\n            <i>dfrA<\/i>\n            genes in lytic phages affects phage and host fitness during infection"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8955-877X","authenticated-orcid":true,"given":"Kai","family":"Wang","sequence":"first","affiliation":[{"name":"National Key Laboratory of Agricultural Microbiology, Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan 430070, Hubei, China."},{"name":"College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9573-2612","authenticated-orcid":true,"given":"Jikai","family":"Xu","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Agricultural Microbiology, Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan 430070, Hubei, China."},{"name":"College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, 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Agricultural Microbiology, Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan 430070, Hubei, China."},{"name":"College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Lu","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Agricultural Microbiology, Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan 430070, Hubei, China."},{"name":"College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haixin","family":"Luo","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Agricultural Microbiology, Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan 430070, Hubei, China."},{"name":"College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, 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