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Rising rates of lincosamide resistance have led to adoption of linezolid as an alternative adjunctive therapy. This report describes a clinical\n                      <jats:italic toggle=\"yes\">S. pyogenes<\/jats:italic>\n                      isolate carrying a multi-drug resistance gene,\n                      <jats:italic toggle=\"yes\">cfr<\/jats:italic>\n                      (C), known to confer the phenicol, lincosamide, oxazolidinone, pleuromutilin, and streptogramin A (PhLOPS\n                      <jats:sub>A<\/jats:sub>\n                      ) resistance phenotype in other bacterial species. Strain GAS-390756 is a pharyngeal isolate collected from a child with pharyngitis in the United States. Whole-genome sequence analysis demonstrated that the isolate belonged to\n                      <jats:italic toggle=\"yes\">emm<\/jats:italic>\n                      type 89 and carried an integrative and conjugative element with\n                      <jats:italic toggle=\"yes\">erm<\/jats:italic>\n                      (B) and\n                      <jats:italic toggle=\"yes\">cfr<\/jats:italic>\n                      (C) cargo genes (ICE\n                      <jats:italic toggle=\"yes\">Spy<\/jats:italic>\n                      390756). Antimicrobial susceptibility testing demonstrated the isolate was resistant to erythromycin and clindamycin but susceptible to linezolid, consistent with the activity of\n                      <jats:italic toggle=\"yes\">erm<\/jats:italic>\n                      (B) but not\n                      <jats:italic toggle=\"yes\">cfr<\/jats:italic>\n                      (C). Comparative analysis of\n                      <jats:italic toggle=\"yes\">cfr<\/jats:italic>\n                      (C)\u2019s genomic context suggested that the promoter sequence may have been lost during ICE\n                      <jats:italic toggle=\"yes\">Spy<\/jats:italic>\n                      390756\u2019s acquisition of the gene. While GAS-390756 remains susceptible to linezolid, the expansion of\n                      <jats:italic toggle=\"yes\">cfr<\/jats:italic>\n                      (C)\u2019s host range into\n                      <jats:italic toggle=\"yes\">S. pyogenes<\/jats:italic>\n                      and its presence on a novel mobile element are concerning. In light of known expression mechanisms for other silent antimicrobial resistance genes, this observation carries epidemiologic and public health importance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      Treatment of severe invasive\n                      <jats:italic toggle=\"yes\">Streptococcus pyogenes<\/jats:italic>\n                      infection has traditionally relied on the adjunctive use of clindamycin with \u03b2-lactam antibiotic therapy. However, rising rates of clindamycin non-susceptibility have led clinicians to adopt linezolid as an alternative therapy. We identified\n                      <jats:italic toggle=\"yes\">S. pyogenes<\/jats:italic>\n                      isolated from a child with pharyngitis that carried the\n                      <jats:italic toggle=\"yes\">cfr<\/jats:italic>\n                      (C) gene. This gene causes resistance to multiple antibiotics, including clindamycin and linezolid, in other bacterial species. At the time of this study, we found no other instances of the\n                      <jats:italic toggle=\"yes\">cfr<\/jats:italic>\n                      (C) gene carried by\n                      <jats:italic toggle=\"yes\">S. pyogenes<\/jats:italic>\n                      in either published reports or the public genome sequence database. While this isolate remained sensitive to linezolid, the expanded host range of\n                      <jats:italic toggle=\"yes\">cfr<\/jats:italic>\n                      (C) found in a novel potentially mobile genomic element may herald the eventual emergence of broader antibiotic resistance in\n                      <jats:italic toggle=\"yes\">S. pyogenes<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/msphere.00277-26","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:03:36Z","timestamp":1787317416000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["A novel integrative and conjugative element in\n                    <i>Streptococcus pyogenes<\/i>\n                    carries a\n                    <i>cfr<\/i>\n                    -like gene associated with linezolid resistance in other species"],"prefix":"10.1128","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8525-7566","authenticated-orcid":true,"given":"Daniel B.","family":"Amusin","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00m6w7z96","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine","place":["Chicago, USA"]},{"id":[{"id":"https:\/\/ror.org\/00m6w7z96","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine","place":["Chicago, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4041-6775","authenticated-orcid":true,"given":"Lacy M.","family":"Simons","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00m6w7z96","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine","place":["Chicago, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dulce S.","family":"Garcia","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00m6w7z96","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine","place":["Chicago, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4596-7939","authenticated-orcid":true,"given":"Alan R.","family":"Hauser","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00m6w7z96","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine","place":["Chicago, USA"]},{"id":[{"id":"https:\/\/ror.org\/00m6w7z96","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine","place":["Chicago, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2314-5213","authenticated-orcid":true,"given":"Emma","family":"Office","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00m6w7z96","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine","place":["Chicago, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0416-5171","authenticated-orcid":true,"given":"Preeti","family":"Jaggi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03czfpz43","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine","place":["Atlanta, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Williams","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03a6zw892","id-type":"ROR","asserted-by":"publisher"}],"name":"Stanley Manne Children\u2019s Research Institute, Ann & Robert H. 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