Limosilactobacillus fermentum Limits Candida glabrata Growth by Ergosterol Depletion.

Candida glabrata is a human-associated opportunistic fungal pathogen. It shares its niche with spp. in the gastrointestinal and vaginal tract. In fact, species are thought to competitively prevent overgrowth. We investigated the molecular aspects of this antifungal effect by analyzing the interaction of C. glabrata strains with Limosilactobacillus fermentum. From a collection of clinical C. glabrata isolates, we identified strains with different sensitivities to in coculture. We analyzed the variation of their expression pattern to isolate the specific response to . C. glabrata- coculture induced genes associated with ergosterol biosynthesis, weak acid stress, and drug/chemical stress. coculture depleted C. glabrata ergosterol. The reduction of ergosterol was dependent on the species, even in coculture with different species. We found a similar ergosterol-depleting effect with other lactobacillus strains (Lactobacillus crispatus and Lactobacillus rhamosus) on Candida albicans, Candida tropicalis, and Candida krusei. The addition of ergosterol improved C. glabrata growth in the coculture. Blocking ergosterol synthesis with fluconazole increased the susceptibility against , which was again mitigated by the addition of ergosterol. In accordance, a C. glabrata mutant, defective in ergosterol biosynthesis, was highly sensitive to . In conclusion, our analysis indicates an unexpected direct function of ergosterol for C. glabrata proliferation in coculture with . The yeast Candida glabrata, an opportunistic fungal pathogen, and the bacterium Limosilactobacillus fermentum both inhabit the human gastrointestinal and vaginal tract. species, belonging to the healthy human microbiome, are thought to prevent C. glabrata infections. We investigated the antifungal effect of Limosilactobacillus fermentum on C. glabrata strains quantitively . The interaction between C. glabrata and evokes an upregulation of genes required for the synthesis of ergosterol, a sterol constituent of the fungal plasma membrane. We found a dramatic reduction of ergosterol in C. glabrata when it was exposed to . This effect extended to other species and other species. Furthermore, fungal growth was efficiently suppressed by a combination of and fluconazole, an antifungal drug which inhibits ergosterol synthesis. Thus, fungal ergosterol is a key metabolite for the suppression of C. glabrata by .