Table 1_Vaginal Lactobacillus paragasseri may attenuate fluconazole-resistant phenotypes in the subset of Candida albicans isolates and shows potential as a probiotic adjunct in antifungal therapy.docx

Guided by established fluconazole-resistance mechanisms, we first screened fluconazole resistant C. albicans isolates by assessing biofilm formation capacity, drug efflux pump gene expression, and ERG11 gene mutations and mRNA expression. Next, analysis of the vaginal Lactobacillus composition in VVC patients and healthy controls showed a nominal, non-significant trend toward lower L. paragasseri detection in VVC-affected women.

Motivated by this trend and by prior evidence that Lactobacilli can modulate antifungal-resistance phenotypes, we examined whether L. paragasseri modulates fluconazole-resistance in clinically derived C. albicans isolates through functional assays. Subsequent functional assessments, including standard antifungal susceptibility testing, biofilm formation assays, and drug efflux pump gene expression analyses.</p>Results<p>Vaginal L. paragasseri can attenuate fluconazole-resistant phenotypes in the tested subset of clinical fluconazole-resistant C. albicans isolates.

In a murine vulvovaginal candidiasis model, adjunctive treatment with L. paragasseri provided adjuvant benefit when added to fluconazole therapy, reducing vaginal C. albicans colonization and alleviating infection-associated tissue damage. These in-vivo observations constitute preliminary pre-clinical evidence.</p>Discussion<p>These findings demonstrate that vaginal L. paragasseri holds promising potential as a probiotic adjunctive therapy for C. albicans-induced VVC, offering novel insights for the development of alternative antifungal therapeutic strategies.</p>