Vaginal *Lactobacillus fermentum* JAC 231 and *L. plantarum* MDBL 269 strains inhibit *Candida albicans* growth and virulence factors.

Vulvovaginal candidiasis (VVC), primarily caused by Candida albicans, affects up to 75% of women of reproductive age. Current therapeutic options face significant challenges due to rising antifungal resistance, host toxicity, and high recurrence rates, highlighting an urgent need for novel strategies. Lactobacillus species, crucial for maintaining a healthy vaginal microbiota, are known for their antagonistic effects against pathogens through antimicrobial metabolite production and immune modulation. However, the specific anti-virulence properties of Lactobacillus strains from asymptomatic women against clinical C. albicans isolates remain underexplored, representing a critical gap in understanding their full therapeutic potential.

Researchers isolated 42 clinical Lactobacillus strains from asymptomatic women and evaluated their antifungal activity against clinical C. albicans isolates. From these, L. fermentum JAC 231 and Lactiplantibacillus plantarum MDBL 269 were selected for detailed analysis, alongside a positive control, L. fermentum ATCC 23271. The study assessed the ability of these strains and their cell-free supernatants (CFS) to interfere with key C. albicans virulence factors, including hyphal morphogenesis, biofilm formation and disruption, adhesion to host cells, and the secretion of extracellular enzymes. Whole-genome sequencing combined with BAGEL4 and antiSMASH tools was used to predict antimicrobial peptide gene clusters.

Out of 42 clinical Lactobacillus isolates, 8 demonstrated inhibitory activity against the tested pathogens. Notably, only L. fermentum JAC 231 and L. plantarum MDBL 269 exhibited broad-spectrum inhibition against all fungal isolates evaluated. Further detailed analysis revealed that these selected strains and their CFS displayed significant antagonistic activities against C. albicans virulence factors. They effectively reduced pathogen adhesion, co-aggregated with yeast cells, and impaired the initial stages of biofilm formation. Importantly, they also destabilized preformed biofilms, indicating a dual action against established fungal communities. Genomic analysis provided insights into potential mechanisms: > L. fermentum JAC 231 was found to possess 2 predicted biosynthetic gene clusters for antimicrobial peptides, while L. plantarum MDBL 269 harbored 7 such clusters, suggesting a robust capacity for producing antimicrobial compounds. These findings underscore the potent anti-Candida and anti-virulence capabilities of specific vaginal Lactobacillus strains.