{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T09:12:48Z","timestamp":1790500368321,"version":"4.1.0"},"reference-count":40,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2018,10,1]],"date-time":"2018-10-01T00:00:00Z","timestamp":1538352000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Microbial Drug Resistance"],"published-print":{"date-parts":[[2018,10]]},"abstract":"\n Although\n mef<\/jats:italic>\n (A) and its subclass\n mef<\/jats:italic>\n (E) genes have long been considered to play a central role in macrolide efflux-based resistance, we have previously demonstrated that the\n msr<\/jats:italic>\n (D) gene located immediately downstream of the\n mef<\/jats:italic>\n (A) gene plays a predominant role in\n Streptococcus pyogenes<\/jats:italic>\n macrolide resistance. The\n mef<\/jats:italic>\n (A) and\n mef<\/jats:italic>\n (E) genes are carried by different genetic elements and the resistance associated with\n mef<\/jats:italic>\n (A) was reported to be higher than that associated with\n mef<\/jats:italic>\n (E); therefore, we further investigated the functional relevance of\n mef<\/jats:italic>\n (A)\/\n mef<\/jats:italic>\n (E) and its associated\n msr<\/jats:italic>\n (D). We established additional\n mef<\/jats:italic>\n (A)-,\n mef<\/jats:italic>\n (E)-, and their associated\n msr<\/jats:italic>\n (D)-knockout strains and confirmed the predominance of\n msr<\/jats:italic>\n (D) over\n mef<\/jats:italic>\n (A)\/\n mef<\/jats:italic>\n (E). In addition, we performed experiments introducing\n mef<\/jats:italic>\n (A),\n mef<\/jats:italic>\n (E), and their associated\n msr<\/jats:italic>\n (D) genes into\n mef<\/jats:italic>\n (A)\/\n mef<\/jats:italic>\n (E)-\n msr<\/jats:italic>\n (D) double-knockout and\n mef<\/jats:italic>\n (A)\/\n mef<\/jats:italic>\n (E) negative strains. Neither\n mef<\/jats:italic>\n (A) nor\n mef<\/jats:italic>\n (E) genes had effects on erythromycin resistance. However, both associated\n msr<\/jats:italic>\n (D) showed significant effects, and the\n mef<\/jats:italic>\n (A)-associated\n msr<\/jats:italic>\n (D) exhibited more effect than the\n mef<\/jats:italic>\n (E)-associated one. These results suggest that an overall functional predominance of\n msr<\/jats:italic>\n (D) over\n mef<\/jats:italic>\n (A)\/\n mef<\/jats:italic>\n (E) is conceivable in efflux-based macrolide resistance in at least some\n S. pyogenes<\/jats:italic>\n strains. Furthermore, the higher resistance of\n mef<\/jats:italic>\n (A) system over\n mef<\/jats:italic>\n (E) system could be derived at least in part from functional differences of\n mef<\/jats:italic>\n (A)- and\n mef<\/jats:italic>\n (E)-associated\n msr<\/jats:italic>\n (D).\n <\/jats:p>","DOI":"10.1089\/mdr.2017.0277","type":"journal-article","created":{"date-parts":[[2018,2,6]],"date-time":"2018-02-06T13:23:52Z","timestamp":1517923432000},"page":"1089-1097","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":24,"title":["Functional Predominance of\n msr<\/i>\n (D), Which Is More Effective as\n mef(<\/i>\n A)-Associated Than\n mef(<\/i>\n E)-Associated, Over\n mef<\/i>\n (A)\/\n mef<\/i>\n (E) in Macrolide Resistance in\n Streptococcus pyogenes<\/i>"],"prefix":"10.1177","volume":"24","author":[{"given":"Ichiro","family":"Tatsuno","sequence":"first","affiliation":[{"name":"Nagoya City University Graduate School of Medical Sciences","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Isaka","sequence":"additional","affiliation":[{"name":"Nagoya City University Graduate School of Medical Sciences","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuaki","family":"Masuno","sequence":"additional","affiliation":[{"name":"Nagoya City University Graduate School of Medical Sciences","place":["Japan"]},{"name":"Nagoya City Public Health Research Institute","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanako","family":"Hata","sequence":"additional","affiliation":[{"name":"Nagoya City University Hospital","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masakado","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Aichi Prefectural Institute of Public Health","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadao","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Nagoya City University Graduate School of Medical Sciences","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2018,10,9]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.13.3.470"},{"key":"e_1_3_3_3_2","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1007\/s10156-004-0360-0","article-title":"Current status of antimicrobial susceptibility of clinical isolates of Streptococcus pyogenes in Japan: report of a countrywide surveillance study","volume":"11","author":"Hotomi M.","year":"2005","unstructured":"Hotomi M., , Billal D.S., , Shimada J., , Yamauchi K., , Fujihara K., , and Yamanaka N.. 2005. Current status of antimicrobial susceptibility of clinical isolates of Streptococcus pyogenes in Japan: report of a countrywide surveillance study. J. Infect. Chemother., 11:48\u201351.","journal-title":"J. Infect. Chemother."},{"key":"e_1_3_3_4_2","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1093\/jac\/dki049","article-title":"Prophage association of mef(A) elements encoding efflux-mediated erythromycin resistance in Streptococcus pyogenes","volume":"55","author":"Giovanetti E.","year":"2005","unstructured":"Giovanetti E., , Brenciani A., , Vecchi M., , Manzin A., , and Varaldo P.E.. 2005. Prophage association of mef(A) elements encoding efflux-mediated erythromycin resistance in Streptococcus pyogenes. J. Antimicrob. Chemother., 55:445\u2013451.","journal-title":"J. Antimicrob. Chemother."},{"key":"e_1_3_3_5_2","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1099\/jmm.0.2008\/002642-0","article-title":"Distribution of emm type and antibiotic susceptibility of group A streptococci causing invasive and noninvasive disease","volume":"57","author":"Wajima T.","year":"2008","unstructured":"Wajima T., , Murayama S.Y., , Sunaoshi K., , Nakayama E., , Sunakawa K., , and Ubukata K.. 2008. Distribution of emm type and antibiotic susceptibility of group A streptococci causing invasive and noninvasive disease. J. Med. Microbiol., 57:1383\u20131388.","journal-title":"J. Med. 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Correlation between genetic features of the mef(A)-msr(D) locus and erythromycin resistance in Streptococcus pyogenes. Diagn. Microbiol. Infect. Dis., 84:57\u201362.","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"e_1_3_3_17_2","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1093\/jac\/dkh481","article-title":"Distribution and molecular analysis of mef(A)-containing elements in tetracycline-susceptible and -resistant Streptococcus pyogenes clinical isolates with efflux-mediated erythromycin resistance","volume":"54","author":"Brenciani A.","year":"2004","unstructured":"Brenciani A., , Ojo K.K., , Monachetti A., , Menzo S., , Roberts M.C., , Varaldo P.E., , and Giovanetti E.. 2004. Distribution and molecular analysis of mef(A)-containing elements in tetracycline-susceptible and -resistant Streptococcus pyogenes clinical isolates with efflux-mediated erythromycin resistance. J. Antimicrob. Chemother., 54:991\u2013998.","journal-title":"J. Antimicrob. 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