The vacuolar fusion regulated by HOPS complex promotes hyphal initiation and penetration in Candida albicans

• Published in: Nature communications 2024-05, Vol.15 (1), p.4131-20, Article 4131
• Main Authors: Liu, Yu, Wang, Ruina, Liu, Jiacun, Fan, Mengting, Ye, Zi, Hao, Yumeng, Xie, Fei, Wang, Ting, Jiang, Yuanying, Liu, Ningning, Cui, Xiaoyan, Lv, Quanzhen, Yan, Lan
• Format: Article
• Language: English
• Subjects: 101/28; 14/34; 38/88; 631/326/193/2542; 64/60; 692/420/254; 692/699/255/1672; 82/1; Animals; Candida albicans; Candida albicans - genetics; Candida albicans - metabolism; Candidiasis - microbiology; Cell cycle; Commensalism; Female; Fungal Proteins - genetics; Fungal Proteins - metabolism; Fusion protein; Humanities and Social Sciences; Hyphae; Hyphae - genetics; Hyphae - growth & development; Hyphae - metabolism; Infections; Kinases; Membrane Fusion; Mice; Morphogenesis; multidisciplinary; Organs; Pathogenicity; Pathogens; Pharmacy; Phenotypes; Protein transport; rab GTP-Binding Proteins - genetics; rab GTP-Binding Proteins - metabolism; Science; Science (multidisciplinary); Signal transduction; Vacuoles; Vacuoles - metabolism; Vesicular Transport Proteins - genetics; Vesicular Transport Proteins - metabolism; Virulence; Yeast; Yeasts
• ISSN: 2041-1723; 2041-1723
• 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 vac8 Δ/Δ and GTR1 OE - vam6 Δ/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. The transition between yeast and hyphae is crucial for the pathogenicity of Candida albicans . Here, Liu et al. show that vacuole fusion is active during hyphal extension and that large vacuoles increase the mechanical forces of hyphae penetrating into organs.