Unveiling the roles of <i>CaSDH8</i> in <i>Candida albicans</i>: Implications for virulence and azole resistance

<i>Candida albicans</i> is the most common pathogen in systemic fungal diseases, exhibits a complex pathogenic mechanism, and is increasingly becoming drug tolerant. Therefore, it is particularly important to study the genes associated with virulence and resistance of <i>C. albicans</i>. Here, we identified a gene (<i>orf19.1588</i>) that encodes a conserved mitochondrial protein known as <i>CaSDH8</i>, upon deletion of <i>CaSdh8</i>, the deleted strain (<i>Casdh8Δ/Δ</i>) experienced impaired growth, hyphal development, and virulence. <i>Casdh8Δ/Δ</i> displayed a reduced capacity to utilize alternative carbon sources, along with detrimental alterations in reactive oxygen species (ROS), mitochondrial membrane potential (MMP) depolarization, and adenosine triphosphate (ATP) levels. Interestingly, <i>Casdh8Δ/Δ</i> demonstrated resistance to azole drugs, and under the influence of fluconazole, the cell membrane permeability and mitochondrial function of <i>Casdh8Δ/Δ</i> were less compromised than those of the wild type, indicating a reduction in the detrimental effects of fluconazole on <i>Casdh8Δ/Δ</i>. These findings highlight the significance of <i>CaSDH8</i> as a crucial gene for the maintenance of cellular homoeostasis. Our study is the first to document the effects of the <i>CaSDH8</i> gene on the virulence and azole resistance of <i>C. albicans</i> at both the molecular and animal levels, providing new clues and directions for the antifungal infection and the discovery of antifungal drug targets.