Distinct Host and Bacterial Profiles in Murine Single Versus Co-Infection with Foal-Isolated Streptococcus equi and Streptococcus dysgalactiae

This study investigated the interactive pathogenic characteristics of co-infection with Streptococcus equi (S. equi) and Streptococcus dysgalactiae (S. dysgalactiae) isolated from diseased foals. Integrating genomic analysis, in vitro phenotypic assays, and a murine intranasal infection model, we comparatively analyzed the biological traits and pathogenic differences between single and dual infections. Comparative genomic analysis revealed divergent virulence profiles between the two isolates, and both species harbored open pan-genomes. In vitro, the biofilm biomass of strain F1 was higher than that of all other groups. No synergistic hemolytic activity was observed in co-cultures of the two isolates. In vivo infection results indicated that streptococcal infection significantly altered the structure and abundance of pulmonary microbiota in mice. Furthermore, single and dual infections displayed strain-specific and time-dependent microbial disparities at early and late infection stages, which were associated with differential enrichment of multiple immune- and metabolism-related Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including the Tumor Necrosis Factor (TNF) and Mitogen-Activated Protein Kinase (MAPK) signaling pathways. Notably, co-infection triggered the most severe pulmonary microbiota dysbiosis and aberrant functional pathway regulation. This study preliminarily characterized the distinct phenotypic and pathological alterations induced by dual streptococcal infection, providing experimental evidence and novel insights for further exploring the interactive features of equine streptococcal mixed infections.