Title (eng)

Limosilactobacillus fermentum Limits Candida glabrata Growth by Ergosterol Depletion


Isabella Zangl   University of Natural Resources and Life Sciences, Vienna

Christoph Schüller   Institute of Microbial Genetics / University of Natural Resources and Life Sciences, Vienna

Joseph Strauss   Institute of Microbial Genetics / University of Natural Resources and Life Sciences, Vienna

Ildiko-Julia Pap   University Hospital of St. Pölten

Roman Labuda   University of Veterinary Medicine, Vienna / University of Natural Resources and Life Sciences, Vienna

Reinhard Beyer   University of Natural Resources and Life Sciences, Vienna

Arianna Gattesco   University of Natural Resources and Life Sciences, Vienna


American Society for Microbiology

Description (eng)

Candida glabrata is a human-associated opportunistic fungal pathogen. It shares its niche with Lactobacillus spp. in the gastrointestinal and vaginal tract. In fact, Lactobacillus species are thought to competitively prevent Candida 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 L. fermentum in coculture. We analyzed the variation of their expression pattern to isolate the specific response to L. fermentum. C. glabrata-L. fermentum coculture induced genes associated with ergosterol biosynthesis, weak acid stress, and drug/chemical stress. L. fermentum coculture depleted C. glabrata ergosterol. The reduction of ergosterol was dependent on the Lactobacillus species, even in coculture with different Candida 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 L. fermentum, which was again mitigated by the addition of ergosterol. In accordance, a C. glabrata Δerg11 mutant, defective in ergosterol biosynthesis, was highly sensitive to L. fermentum. In conclusion, our analysis indicates an unexpected direct function of ergosterol for C. glabrata proliferation in coculture with L. fermentum. IMPORTANCE The yeast Candida glabrata, an opportunistic fungal pathogen, and the bacterium Limosilactobacillus fermentum both inhabit the human gastrointestinal and vaginal tract. Lactobacillus 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 in vitro. The interaction between C. glabrata and L. fermentum 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 L. fermentum. This effect extended to other Candida species and other Lactobacillus species. Furthermore, fungal growth was efficiently suppressed by a combination of L. fermentum and fluconazole, an antifungal drug which inhibits ergosterol synthesis. Thus, fungal ergosterol is a key metabolite for the suppression of C. glabrata by L. fermentum.

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Acid Stress-Response; Lactobacillus-Fermentum; Resistance; Saccharomyces; Genes; Erg11; Bacteria; Albicans; Azoles

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o:605 Publications / University of Veterinary Medicine Vienna