is a dominant in the murine oral mucosa and has chitinase activity that compromises fungal cell wall integrity.

UNLABELLED

The oral microbiome is a critical determinant of health and disease, as interactions between oral microorganisms can influence their physiology and the development or severity of oral infections. Lactobacilli have a widely recognized antagonistic relationship with and may exhibit probiotic properties that limit oral fungal infection. We previously reported that strain MT4, an oral strain isolated from C57BL/6 mice, can induce global changes in the murine oral microbiome and has anti- activity . To build on this information, we analyzed its abundance on the mouse oral mucosa, tested its impact on the severity and progression of oropharyngeal candidiasis (OPC) in a mouse model, and further explored the mechanism of antifungal activity . Our findings reveal that MT4 is a dominant cultivable in the oral mucosa of C57BL/6 mice. Strain MT4 has chitinase activity against , which damages the cell wall and compromises fungal metabolic activity. Oral inoculation with strain MT4 causes a reduction in the -induced rise in the abundance of oral enterococci and oral mucosal damage. This research underscores the potential of strain MT4 as a novel probiotic agent in the prevention or management of OPC, and it contributes to a better understanding of the role of oral bacterial microbiota role in the pathogenesis of fungal infections.

IMPORTANCE

The interactions between the opportunistic pathogen and resident oral bacteria are particularly crucial in maintaining oral health. Emerging antifungal drug-resistant strains, slow-paced drug discovery, and the risk of side effects can compromise the effectiveness of current treatments available for oropharyngeal candidiasis. This study advances the search for alternative microbiome-targeted therapies in oral fungal infections. We report that strain MT4 prevents the -induced bloom of dysbiotic oral enterococci and reduces oral mucosal lesions in an oropharyngeal candidiasis murine model. We also show that this strain directly compromises the cell wall and reduces fungal metabolic activity, partly due to its chitinase activity.