Molecular analysis of Lancefield group C/G streptococci causing human infections in Sheffield, UK

Lancefield group C/G streptococci (GCS/GGS) are increasingly recognized as significant human pathogens that cause a disease spectrum similar to <i>Streptococcus pyogenes</i>. Despite their high clinical burden in the UK, their genomic diversity remains poorly understood. We performed whole-genome sequencing on a prospective collection of 109 consecutive GCS/GGS isolates from any infection types in Sheffield, UK, over 5 months in 2020. <i>Streptococcus dysgalactiae</i> subsp. <i>equisimilis</i> (SDSE) accounted for 104 isolates, while 5 were identified as <i>Streptococcus canis</i>. The SDSE population was highly diverse, comprising 15 genomic clusters and 38 unique <i>emm</i>-ST combinations. We identified the presence of the ST20/stG62647 international lineage (24% of isolates), a cluster globally associated with severe invasive disease. Antimicrobial resistance genes were prevalent (49%), predominantly linked to mobile genetic elements carrying tetracycline and macrolide resistance. Furthermore, a variation in the penicillin-binding protein PBP2X (P601L) was linked to reduced penicillin sensitivity (minimum inhibitory concentration 0.03 mg l^-1). There were few or no genetic changes in isolates obtained from the same patient, even when they were collected 8-10 weeks apart, indicating long-term persistence within a host. The unexpected detection of <i>S. canis</i> in human infections and the high diversity of SDSE, persistence and virulence-associated regions underscore the need for enhanced national genomic surveillance to track emerging virulent and antibiotic-resistant SDSE lineages.