Genomic Characterization and Classification of Streptococcus oralis Using Next-Generation Sequencing ^†

Streptococcus oralis is an alpha-hemolytic, Gram-positive bacterium from the viridans group streptococci (VGS). While commonly part of the normal oral flora, its role in extraoral infections is increasingly recognized. Reported infections include endocarditis, meningitis, and urinary tract infections (UTIs). In this study, we describe a rare case of a S. oralis-associated UTI in an 83-year-old male with a history of recurrent infections. Genomic characterization using short- and long-read sequencing revealed multiple virulence factors and antimicrobial resistance determinants. The isolate was resistant to cefepime and ceftriaxone, an uncommon phenotype in S. oralis. Key virulence genes detected included nanA, ribX, speA, scpB, and lytB. Phylogenetic analysis showed high sequence similarity to S. oralis subsp. oralis and S. oralis subsp. dentisani. Importantly, we also identified homologs of the Type VII Secretion System (T7SS) components EssC and EsxA, supported by PFAM domain analysis and phylogenetic clustering within canonical T7SS lineages. Ongoing work is focused on characterizing the genetic context of these T7SS-associated genes to better understand their regulation and potential role in virulence. These findings will expand current knowledge of S. oralis pathogenicity and highlight the value of genomic surveillance in detecting emerging virulence pathways in VGS members.