{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:37:59Z","timestamp":1785411479070,"version":"3.56.0"},"reference-count":39,"publisher":"American Society for Microbiology","license":[{"start":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T00:00:00Z","timestamp":1749686400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T00:00:00Z","timestamp":1749686400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31970075, U20A2040"],"award-info":[{"award-number":["31970075, U20A2040"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Phage-plasmids carry a significant burden of clinically relevant antibiotic resistance genes (ARGs). Intriguingly, the majority of these ARGs are found within plasmids with phage features, with a single exception residing in a phage genome with plasmid features. Therefore, we speculate that phage genomes with plasmid features, whose sequences are highly homologous to bacterial plasmids, may carry novel ARGs. We subsequently identified 46 such phage genomes by employing Hidden Markov models (HMMs) based on plasmid-specific protein profiles andbasic local alignment search tool (BLASTn) searches against the National Center for Biotechnology Information (NCBI) RefSeq Plasmid Database. Among them, six phages harbored seven ARGs identified through a lenient-threshold search strategy, of which only two had been previously reported. The remaining five ARGs were categorized as novel ARGs since their encoded proteins differed from known ARGs. Notably, half of the phages carried trimethoprim-resistant\n                      <jats:italic toggle=\"yes\">dfrA<\/jats:italic>\n                      -like genes. Functional studies characterized these genes and demonstrated that the expression of two of these\n                      <jats:italic toggle=\"yes\">dfrA<\/jats:italic>\n                      genes (\n                      <jats:italic toggle=\"yes\">dfrA50<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">dfrA51<\/jats:italic>\n                      ) can confer resistance to trimethoprim in\n                      <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                      . Through genome analysis, we found that these phages with plasmid features likely contributed to the natural dissemination of these\n                      <jats:italic toggle=\"yes\">dfrA<\/jats:italic>\n                      genes, as evidenced by their widespread presence in plasmids across various pathogenic bacteria. These findings underscore the importance of identifying and monitoring ARGs encoded by phage genomes with plasmid features that also function as plasmids in bacteria, aiming to proactively address the antibiotic resistance challenges posed by these phage-mediated dissemination events.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01695-24","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T09:17:32Z","timestamp":1749719852000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Two novel trimethoprim resistance genes,\n                    <i>dfra50<\/i>\n                    and\n                    <i>dfra51<\/i>\n                    , identified in phage-plasmids"],"prefix":"10.1128","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8955-877X","authenticated-orcid":false,"given":"Kai","family":"Wang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02sp3q482","id-type":"ROR","asserted-by":"publisher"}],"name":"National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University","place":["Wuhan, China"]},{"id":[{"id":"https:\/\/ror.org\/023b72294","id-type":"ROR","asserted-by":"publisher"}],"name":"College of Life Science and Technology, Huazhong Agricultural University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jikai","family":"Xu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02sp3q482","id-type":"ROR","asserted-by":"publisher"}],"name":"National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University","place":["Wuhan, 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Identification and characterization of two novel ISCR1-associated genes dfrA42 and dfrA43 encoding trimethoprim resistant dihydrofolate reductases. 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