Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), School of Pharmacy, Naval Medical University, Shanghai, 200433, PR China.
School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200241, PR China.
Nat Commun. 2024 May 16;15(1):4131. doi: 10.1038/s41467-024-48525-5.
The transition between yeast and hyphae is crucial for regulating the commensalism and pathogenicity in Candida albicans. The mechanisms that affect the invasion of hyphae in solid media, whose deficiency is more related to the pathogenicity of C. albicans, have not been elucidated. Here, we found that the disruption of VAM6 or VPS41 which are components of the homotypic vacuolar fusion and protein sorting (HOPS) complex, or the Rab GTPase YPT72, all responsible for vacuole fusion, led to defects in hyphal growth in both liquid and solid media, but more pronounced on solid agar. The phenotypes of vac8Δ/Δ and GTR1-vam6Δ/Δ mutants indicated that these deficiencies are mainly caused by the reduced mechanical forces that drive agar and organs penetration, and confirmed that large vacuoles are required for hyphal mechanical penetration. In summary, our study revealed that large vacuoles generated by vacuolar fusion support hyphal penetration and provided a perspective to refocus attention on the role of solid agar in evaluating C. albicans invasion.
酵母和菌丝体之间的转换对于调节白色念珠菌的共生和致病性至关重要。影响固体培养基中菌丝体入侵的机制尚未阐明，而菌丝体入侵的缺乏与白色念珠菌的致病性更为相关。在这里，我们发现，破坏同源空泡融合和蛋白质分选（HOPS）复合物的组成部分 VAM6 或 VPS41，或 Rab GTPase YPT72，都负责空泡融合，导致菌丝体在液体和固体培养基中生长缺陷，但在固体琼脂中更为明显。vac8Δ/Δ 和 GTR1-vam6Δ/Δ 突变体的表型表明，这些缺陷主要是由于驱动琼脂和器官穿透的机械力减少所致，并证实大空泡对于菌丝体的机械穿透是必需的。总之，我们的研究表明，空泡融合产生的大空泡支持菌丝体穿透，并为重新关注固体琼脂在评估白色念珠菌入侵中的作用提供了一个视角。
