{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T21:52:48Z","timestamp":1783288368033,"version":"3.54.6"},"reference-count":26,"publisher":"Microbiology Society","issue":"6","license":[{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"crossref","award":["11\/72\/01"],"award-info":[{"award-number":["11\/72\/01"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"crossref","award":["13\/88\/21"],"award-info":[{"award-number":["13\/88\/21"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100007901","name":"Microbiology Society","doi-asserted-by":"crossref","award":["GA003510"],"award-info":[{"award-number":["GA003510"]}],"id":[{"id":"10.13039\/501100007901","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["NU-015900"],"award-info":[{"award-number":["NU-015900"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,3]]},"abstract":"<jats:p>\n                  <jats:bold>Introduction.<\/jats:bold> The antibiotic trimethoprim has been used to treat urinary tract infection (UTI) since ~1962. Alongside the nitrofurantoin, there are still justified reasons for trimethoprim use, especially in non-pregnant women. Trimethoprim resistance is commonly the result of acquiring the trimethoprim-insensitive dihydrofolate reductase gene: <jats:italic>dfrA<\/jats:italic>. Assessment of clinical <jats:italic>Escherichia coli<\/jats:italic> isolates from two clinical trials, AnTIC and ALTAR, identified carriage of two copies of <jats:italic>dfrA<\/jats:italic>.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Hypothesis.<\/jats:bold> The hypothesis tested here was that dual <jats:italic>dfrA<\/jats:italic> carriage provided <jats:italic>E. coli<\/jats:italic> with a growth advantage.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Methodology.<\/jats:bold> Two hundred and seventy-eight clinical isolates from AnTIC\/ALTAR were assessed for <jats:italic>dfrA<\/jats:italic> carriage. Microplate-based growth assays assessed growth behaviour with and without 64\u2009mg\u2009l<jats:sup>\u22121<\/jats:sup> trimethoprim. Allelic replacement of <jats:italic>dfrA5<\/jats:italic> with five other alleles was also performed.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Results.<\/jats:bold> One hundred and four isolates (37%) were identified to carry a total of 112 <jats:italic>dfrA<\/jats:italic> genes. Eight isolates (2.9%) carried two copies of <jats:italic>dfrA<\/jats:italic>. Comparison of <jats:italic>dfrA<\/jats:italic>\n                  <jats:sup>+<\/jats:sup> to dual <jats:italic>dfrA<\/jats:italic> carriage could be differentiated by their growth behaviour when exposed to trimethoprim but had comparable MIC (&gt;512\u2009mg\u2009l<jats:sup>\u22121<\/jats:sup>). Analysis of all <jats:italic>dfrA<\/jats:italic>\n                  <jats:sup>+<\/jats:sup> isolates determined that the growth behaviour exhibited an allelic bias. Allelic replacement of <jats:italic>dfrA5<\/jats:italic> with <jats:italic>dfrA1<\/jats:italic>, <jats:italic>dfrA7<\/jats:italic>, <jats:italic>dfrA8<\/jats:italic>, <jats:italic>dfrA14<\/jats:italic> and <jats:italic>dfrA17<\/jats:italic> demonstrated that the growth behaviour was <jats:italic>dfrA<\/jats:italic> specific.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Conclusion.<\/jats:bold> This analysis determined that the dual carriage of two <jats:italic>dfrA<\/jats:italic> alleles generated a growth advantage to <jats:italic>E. coli<\/jats:italic>. However, the growth behaviour was dictated by allele carriage and not specifically dual carriage, as single carriage isolates also possessed the identified phenotype. This data suggests that there is a potential clinical impact dictated by <jats:italic>dfrA<\/jats:italic> allele carriage that could improve clinical decisions on management strategies of UTI.<\/jats:p>","DOI":"10.1099\/jmm.0.002021","type":"journal-article","created":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T12:17:25Z","timestamp":1748953045000},"source":"Crossref","is-referenced-by-count":3,"title":["Trimethoprim resistance in Escherichia coli exhibits an allele-specific growth advantage"],"prefix":"10.1099","volume":"74","author":[{"given":"Alexandra","family":"Spencer","sequence":"first","affiliation":[{"name":"Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qixiang","family":"Wong","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Nutrition and Sport Sciences, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, 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