The AAA ATPase Vps4 Plays Important Roles in Candida albicans Hyphal Formation and is Inhibited by DBeQ
Candida albicans is an opportunistic human pathogen, and its pathogenicity is associated with hyphal formation. Previous studies have shown that at neutral-to-alkaline pH, hyphal growth is dependent on the Rim101 pathway whose activation requires Snf7, a member of the ESCRT system. In this work, we described the purification and characterization of the C. albicans Vps4, an AAA ATPase required for recycling of the ESCRTs. Its role on hyphal growth has been investigated. Our data suggest deletion of Vps4 decreases overall hyphal growth at pH 7 and increases the growth of multiple hyphae induced by serum, which indicates that the ESCRTs may make a Rim101-independent contribution to hyphal growth. Furthermore, DBeQ, an inhibitor of the AAA ATPase p97, was shown to inhibit the ATPase activity of Vps4 with an IC50 of about 11.5 μM. To a less degree, it also inhibits hyphal growth. Our work may provide a new strategy to control C. albicans infection.
KeywordsESCRT Vps4 Candida albicans Hyphal Polarity DBeQ
This work is supported by grants from the Fok Ying Tung Education Foundation (#132025), the National Science Foundation of China (#31070682), the Fundamental Research Funds for the Central Universities, the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry, the Program of the Co-Construction with Beijing Municipal Commission of Education of China and the Beijing Natural Science Foundation (#5154029).
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