{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T10:41:44Z","timestamp":1776940904207,"version":"3.51.4"},"reference-count":41,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T00:00:00Z","timestamp":1396310400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The use of trimethoprim in treatment of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Streptococcus pyogenes<\/jats:named-content>\n            infections has long been discouraged because it has been widely believed that this pathogen is resistant to this antibiotic. To gain more insight into the extent and molecular basis of trimethoprim resistance in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. pyogenes<\/jats:named-content>\n            , we tested isolates from India and Germany and sought the factors that conferred the resistance. Resistant isolates were identified in tests for trimethoprim or trimethoprim-sulfamethoxazole (SXT) susceptibility. Resistant isolates were screened for the known horizontally transferable trimethoprim-insensitive dihydrofolate reductase (\n            <jats:italic>dfr<\/jats:italic>\n            ) genes\n            <jats:italic>dfrG<\/jats:italic>\n            ,\n            <jats:italic>dfrF<\/jats:italic>\n            ,\n            <jats:italic>dfrA<\/jats:italic>\n            ,\n            <jats:italic>dfrD<\/jats:italic>\n            , and\n            <jats:italic>dfrK<\/jats:italic>\n            . The nucleotide sequence of the intrinsic\n            <jats:italic>dfr<\/jats:italic>\n            gene was determined for resistant isolates lacking the horizontally transferable genes. Based on tentative criteria, 69 out of 268 isolates (25.7%) from India were resistant to trimethoprim. Occurring in 42 of the 69 resistant isolates (60.9%),\n            <jats:italic>dfrF<\/jats:italic>\n            appeared more frequently than\n            <jats:italic>dfrG<\/jats:italic>\n            (23 isolates; 33.3%) in India. The\n            <jats:italic>dfrF<\/jats:italic>\n            gene was also present in a collection of SXT-resistant isolates from Germany, in which it was the only detected trimethoprim resistance factor. The\n            <jats:italic>dfrF<\/jats:italic>\n            gene caused resistance in 4 out of 5 trimethoprim-resistant isolates from the German collection. An amino acid substitution in the intrinsic dihydrofolate reductase known from trimethoprim-resistant\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Streptococcus pneumoniae<\/jats:named-content>\n            conferred resistance to\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. pyogenes<\/jats:named-content>\n            isolates of\n            <jats:italic>emm<\/jats:italic>\n            type 102.2, which lacked other aforementioned\n            <jats:italic>dfr<\/jats:italic>\n            genes. Trimethoprim may be more useful in treatment of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. pyogenes<\/jats:named-content>\n            infections than previously thought. However, the factors described herein may lead to the rapid development and spread of resistance of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. pyogenes<\/jats:named-content>\n            to this antibiotic agent.\n          <\/jats:p>","DOI":"10.1128\/aac.02282-13","type":"journal-article","created":{"date-parts":[[2014,2,4]],"date-time":"2014-02-04T04:05:07Z","timestamp":1391486707000},"page":"2281-2288","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":37,"title":["Factors That Cause Trimethoprim Resistance in Streptococcus pyogenes"],"prefix":"10.1128","volume":"58","author":[{"given":"Ren\u00e9","family":"Bergmann","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"van der Linden","sequence":"additional","affiliation":[{"name":"German National Reference Center for Streptococci, Department of Medical Microbiology, University Hospital RWTH Aachen, Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gursharan S.","family":"Chhatwal","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. Patric","family":"Nitsche-Schmitz","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.2.279"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.106.3.856-862.1971"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1089\/107662903765826732"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.5.1062"},{"key":"e_1_3_2_6_2","first-page":"63","article-title":"Synergy of trimethoprim-sulfamethoxazole","volume":"112","author":"Bushby SR","year":"1975","unstructured":"BushbySR. 1975. Synergy of trimethoprim-sulfamethoxazole. Can. Med. Assoc. J. 112:63\u201366.","journal-title":"Can. Med. Assoc. 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