An outbreak of scarlet fever began in mainland China and Hong Kong in 2011. Macrolide and tetracycline resistant Streptococcus pyogenes emm12 represent the majority of isolates. The next most common scarlet fever isolates were S. pyogenes emm1.
By employing Illumina and PacBio sequence analysis, two mobile genetic elements were found closely associated with emm12 outbreak isolates: the integrative and conjugative element ICE-emm12 encoding tetracycline and macrolide resistance, and prophage ΦHKU.vir encoding superantigens SSA and SpeC, and DNase Spd1.
Genomic interrogation of 141 emm12 isolates revealed the introduction of several ICE-emm12 variants, ΦHKU.vir and a novel prophage, ΦHKU.ssa, occurred into three distinct emm12 lineages late in the 20th century triggering the expansion of scarlet fever associated emm12 clones in Hong Kong. Genomic analysis of 34 emm1 isolates identified the presence of ICE-emm12 and ΦHKU.vir in an M1T1 genomic background, conferring expression of superantigens SSA and SpeC, and resistance to tetracycline, erythromycin and clindamycin.
The horizontal transfer of ICE-emm12 and ΦHKU.vir, leading to resistance against macrolide antibiotics and expression of an enhanced superantigen repertoire in clinically important group A streptococcal serotypes, should prompt heightened surveillance for the global dissemination of these genetic elements.