{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T14:25:48Z","timestamp":1778509548993,"version":"3.51.4"},"reference-count":19,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T00:00:00Z","timestamp":1649203200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16K08782"],"award-info":[{"award-number":["16K08782"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Microbiology and Immunology"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The <jats:italic>mef<\/jats:italic>(A)\u2010 and its subclass <jats:italic>mef<\/jats:italic>(E) systems had long been considered to constitute one of the primary macrolide\u2010resistant mechanisms in <jats:italic>Streptococcus pyogenes<\/jats:italic>. However, we have previously demonstrated that the <jats:italic>msr<\/jats:italic>(D) gene located immediately downstream of the <jats:italic>mef<\/jats:italic>(A)\/<jats:italic>mef<\/jats:italic>(E) genes plays a predominant role in these systems. In previous studies, furthermore, <jats:italic>mef<\/jats:italic>(A)\u2010associated <jats:italic>msr<\/jats:italic>(D)<jats:sub>10\u201085<\/jats:sub> of an <jats:italic>S. pyogenes<\/jats:italic> strain (10\u201085) exhibited a greater increase in clarithromycin minimum inhibitory concentration (MIC) than <jats:italic>mef<\/jats:italic>(E)\u2010associated <jats:italic>msr<\/jats:italic>(D)<jats:sub>13\u2010O\u201010<\/jats:sub> of another strain (13\u2010O\u201010). Both <jats:italic>msr<\/jats:italic>(D) genes encode 487 amino acid residues, 13 amino acid residues of which are different from each other. In this study, we performed mutational analysis of the <jats:italic>msr<\/jats:italic>(D) genes and showed that a single\u2010nucleotide polymorphism to cause a substitution of Asp238 with Gly is mainly associated with the greater increase in clarithromycin MIC by the <jats:italic>msr<\/jats:italic>(D)<jats:sub>10\u201085<\/jats:sub> than by the <jats:italic>msr<\/jats:italic>(D)<jats:sub>13\u2010O\u201010<\/jats:sub> allele. In addition, another substitution of Ser with Arg at codon 194 is partially associated with the greater increase by the <jats:italic>msr<\/jats:italic>(D)<jats:sub>10\u201085<\/jats:sub> than by the <jats:italic>msr<\/jats:italic>(D)<jats:sub>13\u2010O\u201010<\/jats:sub> allele.<\/jats:p>","DOI":"10.1111\/1348-0421.12974","type":"journal-article","created":{"date-parts":[[2022,3,3]],"date-time":"2022-03-03T13:53:49Z","timestamp":1646315629000},"page":"299-306","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A greater effect on clarithromycin resistance of <i>mef<\/i>(A)\u2010associated <i>msr<\/i>(D) than <i>mef<\/i>(E)\u2010associated <i>msr<\/i>(D) in <i>Streptococcus pyogenes<\/i>"],"prefix":"10.1111","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4053-9695","authenticated-orcid":false,"given":"Ichiro","family":"Tatsuno","sequence":"first","affiliation":[{"name":"Department of Bacteriology 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