A new fungal taurine biosynthetic pathway promotes metabolic fitness and virulence in Candida albicans
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Taurine is an abundant sulfur-containing metabolite with diverse roles in cellular physiology across many organisms, yet its biosynthesis and biological functions remain largely unexplored in fungi. Here, we provide evidence for endogenous taurine production in the major human fungal pathogen Candida albicans and identify Csd1, a cysteine sulfinic acid decarboxylase (CSAD)-related protein, as a major determinant of this process. Loss of CSD1 nearly abolished intracellular taurine and caused extensive remodeling of sulfur metabolism, including cysteine accumulation and altered abundance of methionine-cycle metabolites. Consistent with these metabolic defects, csd1 cells exhibited impaired growth and increased sensitivity to cysteine, oxidative and osmotic stresses, elevated temperature, reactive sulfur species, and the antifungal drugs amphotericin B and caspofungin. Exogenous taurine selectively rescued a subset of these phenotypes, indicating that CSD1 loss causes both taurine-dependent and broader metabolic defects. Csd1 was also required for normal hyphal morphogenesis, and csd1 cells displayed markedly attenuated virulence in a Galleria mellonella systemic infection model. Comparative sequence analysis revealed conservation of key features of the pyridoxal 5′-phosphate-dependent catalytic machinery shared with mammalian and bacterial CSADs, together with divergence within the predicted substrate-recognition pocket. Our genetic data further suggest that taurine production in C. albicans differs from the canonical metazoan cysteine sulfinic acid pathway and may involve branched or redundant routes. Together, these findings establish endogenous taurine production as a new facet of fungal sulfur metabolism and identify Csd1-dependent metabolism as an important contributor to sulfur homeostasis, stress adaptation, morphogenesis, and pathogenic fitness in C. albicans .
Author Summary
Taurine is a sulfur-containing molecule abundant in animals, where it contributes to numerous physiological processes. Although taurine has also been detected in fungi, whether fungi can synthesize it and what biological functions it might serve have remained poorly understood. Here, we show that the highly prevalent human fungal pathogen Candida albicans produces taurine and identify Csd1 as a protein required for efficient taurine production. Cells lacking CSD1 contained almost no taurine and showed broad alterations in sulfur metabolism, including cysteine accumulation. These cells grew poorly and were more vulnerable to several environmental stresses and antifungal drugs. They were also defective in forming hyphae, a growth form associated with C. albicans pathogenicity, and were markedly less virulent in an infection model. Interestingly, supplying taurine restored some, but not all, of these defects, indicating that loss of CSD1 affects both taurine production and broader sulfur metabolic homeostasis. Our findings establish taurine biosynthesis as a new facet of fungal sulfur metabolism and reveal its importance for the ability of C. albicans to adapt to stressful conditions and maintain pathogenic fitness.
