Mitochodrial anchor protein affects virulence of Candida albicans

Candida albicans is a major cause of fungal infections in humans and plays a significant role in fungal-related deaths due to its ability to form filaments and mask its cell wall, which are controlled by multiple signaling pathways. However, the relationship between mitochondria, filamentation, and cell wall masking in C. albicans is not fully understood. Therefore, we first determined that the mitochondrial anchor protein Num11 greatly affects filamentation and cell wall masking in C. albicans, both of which are crucial factors for infection. We then discovered that the loss of Num11 increases the ingestion of macrophages and decreases pathogenic activities in vivo. Interestingly, we found that the anchor protein Num1 can regulate the cAMP-PKA pathway to promote the growth of hyphal forms, influencing the Cdc42-Cek1 MAPK pathway to affect the production and presentation of polysaccharide components in the cell wall. Through these powerful mechanisms, the mitochondrial anchor protein Num11 significantly contributes to the pathogenicity of C. albicans. Our research also highlights the potential of Num1 as a new target for antifungal agents in the face of the ongoing challenge of drug-resistant fungi.白色念珠菌（Candida albicans）是人类真菌感染的主要致病菌，因其能够形成菌丝并掩盖细胞壁（该过程受多条信号通路调控），故而在真菌相关死亡事件中发挥着重要作用。然而，目前学界尚未完全阐明白色念珠菌中线粒体、菌丝形成与细胞壁掩盖三者之间的调控关联。为此，本研究首先证实，线粒体锚定蛋白Num11可显著影响白色念珠菌的菌丝形成与细胞壁掩盖过程——这二者均为感染致病的关键因素。随后研究发现，Num11的缺失会增强巨噬细胞对其的吞噬作用，并降低其体内致病活性。值得注意的是，本研究还发现锚定蛋白Num1可通过调控cAMP-PKA信号通路（cAMP-PKA pathway）以促进菌丝形态的生长，同时通过影响Cdc42-Cek1丝裂原活化蛋白激酶（MAPK）通路，调控细胞壁多糖组分的合成与呈递。通过上述多重作用机制，线粒体锚定蛋白Num11可显著增强白色念珠菌的致病性。本研究同时指出，面对日益严峻的真菌耐药性挑战，Num1有望成为抗真菌剂（antifungal agents）的全新作用靶点。