A fungal pathobiont promotes Streptococcus vaginal persistence and pathogenesis through physical and metabolic interactions.

Group B Streptococcus (GBS) frequently colonizes the vagina asymptomatically, where the bacterium interacts with a complex microbial community. During pregnancy, colonization can trigger adverse outcomes and neonatal invasive infection. Using an adapted murine model of vaginal colonization, we show that the human pathobiont Candida albicans supports GBS fitness in the vaginal tract and ascension to the uterus. C. albicans positively associates with GBS across several human studies, and C. albicans and GBS physically interact in a mouse co-colonization model. This co-colonization contributes to GBS persistence in the vagina, cervix, and uterus and facilitates antibiotic evasion. Across clinical isolates, the hyphal form of C. albicans promotes GBS aggregation and adhesion to host epithelial cells. Contact with GBS induces arginine biosynthesis in C. albicans, which drives bacterial virulence gene expression and primes GBS adhesion. These findings show that interkingdom nutrient exchange can increase GBS pathogenic potential and highlight targets for preventive therapies.