MSS2 maintains mitochondrial function and is required for chitosan resistance, invasive growth, biofilm formation and virulence in Candida albicans

Candida albicans is the most prevalent fungal pathogen in humans, particularly in immunocompromised patients. In this study, by screening a C. albicans mutant library, we first identified that the MSS2 gene, an ortholog of Saccharomyces cerevisiae MSS2 required for mitochondrial respiration, mediates chitosan resistance. Upon treatment with 0.2% chitosan, the growth of mss2Δ strains was strikingly impaired, and MSS2 expression was significantly repressed by chitosan. Furthermore, mss2Δ strains exhibited slow growth on medium supplemented with glycerol as the sole carbon source. Similar to the chitosan-treated wild-type strain, the mss2Δ strain exhibited a significantly impaired ATP production ability. These data suggest that an antifungal mechanism of chitosan against C. albicans acts by inhibiting MSS2 gene expression, leading to repression of mitochondrial function. Normal respiratory function is suggested to be required for fungal virulence. Interestingly, the mss2Δ mutant strains exhibited significantly impaired invasive ability in vitro and ex vivo but retained normal hyphal development ability in liquid medium. Furthermore, the MSS2 deletion strains could not form robust biofilms and exhibited significantly reduced virulence. Collectively, these results demonstrated that the antifungal effect of chitosan against C. albicans is mediated via inhibition of mitochondrial biogenesis. These data may provide another strategy for antifungal drug development via inhibition of fungal mitochondria. ? 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.