Population genomics of an accidental pathogen Streptococcus mitis from patients with bloodstream infection and infective endocarditis in the UK and Ireland

Abstract Streptococcus mitis is a leading cause of infective endocarditis (IE). However, our understanding of the genomic epidemiology and pathogenicity of IE-associated S. mitis is hampered by low IE incidence. Here we use whole genome sequencing of 217 S. mitis bloodstream infection (BSI) isolates collected between 2001–2016 from clinically diagnosed IE cases in the UK to investigate genetic diversity, antimicrobial resistance, and pathogenicity. We show high genetic diversity of IE-associated S. mitis with virtually all isolates belonging to distinct lineages indicating no predominance of specific lineages. Additionally, we found a highly variable distribution of known pneumococcal virulence genes among the isolates, some of which were overrepresented in the disease than contextual carriage strains. Our findings suggest that S. mitis in patients with clinically diagnosed IE is not primarily caused by specific hypervirulent or antimicrobial resistant lineages, highlighting the accidental pathogen nature of S. mitis in patients with clinically diagnosed IE.