Enhanced nasopharyngeal infection and shedding associated with an epidemic lineage of emm3 group A Streptococcus

Abstract

This research was funded by UKCRC (UK Clinical Research Collaboration, Centre for Infection Prevention and Management) and National Institute of Health Research for Health Protection Research (NIHR CHPR) programme (project number: 106846/107513). The research was also supported by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Healthcare Associated Infections and AMR at Imperial College London in partnership with Public Health England (PHE).Background :  A group A Streptococcus (GAS) lineage of genotype emm3, sequence type 15 (ST15) was associated with a six month upsurge in invasive GAS disease in the UK. The epidemic lineage (Lineage C) had lost two typical emm3 prophages, Φ315.1 and Φ315.2 associated with the superantigen ssa, but gained a different prophage (ΦUK-M3.1) associated with a different superantigen, speC and a DNAse spd1. Methods and Results :  The presence of speC and spd1 in Lineage C ST15 strains enhanced both in vitro mitogenic and DNAse activities over non-Lineage C ST15 strains. Invasive disease models in Galleria mellonella and SPEC-sensitive transgenic mice, revealed no difference in overall invasiveness of Lineage C ST15 strains compared to non-Lineage C ST15 strains, consistent with clinical and epidemiological analysis. Lineage C strains did however markedly prolong murine nasal infection with enhanced nasal and airborne shedding compared to non-Lineage C strains. Deletion of speC or spd1 in two Lineage C strains identified a possible role for spd1 in airborne shedding from the murine nasopharynx. Conclusions:   Nasopharyngeal infection and shedding of Lineage C strains was enhanced compared to non-Lineage C strains and this was, in part, mediated by the gain of the DNase spd1 through prophage acquisition.Peer reviewe