A novel integrative and conjugative element in Streptococcus pyogenes carries a cfr -like gene associated with linezolid resistance in other species

ABSTRACT Treatment of severe invasive Streptococcus pyogenes infections has historically relied on β-lactam antibiotics with adjunctive clindamycin. Rising rates of lincosamide resistance have led to adoption of linezolid as an alternative adjunctive therapy. This report describes a clinical S. pyogenes isolate carrying a multi-drug resistance gene, cfr (C), known to confer the phenicol, lincosamide, oxazolidinone, pleuromutilin, and streptogramin A (PhLOPS A ) 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 emm type 89 and carried an integrative and conjugative element with erm (B) and cfr (C) cargo genes (ICE Spy 390756). Antimicrobial susceptibility testing demonstrated the isolate was resistant to erythromycin and clindamycin but susceptible to linezolid, consistent with the activity of erm (B) but not cfr (C). Comparative analysis of cfr (C)’s genomic context suggested that the promoter sequence may have been lost during ICE Spy 390756’s acquisition of the gene. While GAS-390756 remains susceptible to linezolid, the expansion of cfr (C)’s host range into S. pyogenes 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. IMPORTANCE Treatment of severe invasive Streptococcus pyogenes infection has traditionally relied on the adjunctive use of clindamycin with β-lactam antibiotic therapy. However, rising rates of clindamycin non-susceptibility have led clinicians to adopt linezolid as an alternative therapy. We identified S. pyogenes isolated from a child with pharyngitis that carried the cfr (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 cfr (C) gene carried by S. pyogenes in either published reports or the public genome sequence database. While this isolate remained sensitive to linezolid, the expanded host range of cfr (C) found in a novel potentially mobile genomic element may herald the eventual emergence of broader antibiotic resistance in S. pyogenes .