title: The AAA ATPase Vps4 Plays Important Roles in Candida albicans Hyphal Formation and is Inhibited by DBeQ.
abstract: 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.
authors.affiliation: Gene Engineering and Biotechnology Beijing Key Laboratory, College of Life Sciences, Beijing Normal University, Beijing, 100875, China.
authors.forename: Yahui
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing, 100875, China.
authors.forename: Wanjie
authors.initials: W
authors.lastname: Li
authors.affiliation: Gene Engineering and Biotechnology Beijing Key Laboratory, College of Life Sciences, Beijing Normal University, Beijing, 100875, China.
authors.forename: Mi
authors.initials: M
authors.lastname: Chu
authors.affiliation: Gene Engineering and Biotechnology Beijing Key Laboratory, College of Life Sciences, Beijing Normal University, Beijing, 100875, China.
authors.forename: Hengye
authors.initials: H
authors.lastname: Chen
authors.affiliation: Gene Engineering and Biotechnology Beijing Key Laboratory, College of Life Sciences, Beijing Normal University, Beijing, 100875, China.
authors.forename: Haoyuan
authors.initials: H
authors.lastname: Yu
authors.affiliation: Gene Engineering and Biotechnology Beijing Key Laboratory, College of Life Sciences, Beijing Normal University, Beijing, 100875, China.
authors.forename: Chaoguang
authors.initials: C
authors.lastname: Fang
authors.affiliation: Gene Engineering and Biotechnology Beijing Key Laboratory, College of Life Sciences, Beijing Normal University, Beijing, 100875, China.
authors.forename: Ningze
authors.initials: N
authors.lastname: Sun
authors.affiliation: Gene Engineering and Biotechnology Beijing Key Laboratory, College of Life Sciences, Beijing Normal University, Beijing, 100875, China.
authors.forename: Qiming
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Gene Engineering and Biotechnology Beijing Key Laboratory, College of Life Sciences, Beijing Normal University, Beijing, 100875, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Luo
authors.affiliation: Gene Engineering and Biotechnology Beijing Key Laboratory, College of Life Sciences, Beijing Normal University, Beijing, 100875, China.
authors.forename: Kaiju
authors.initials: K
authors.lastname: Luo
authors.affiliation: Gene Engineering and Biotechnology Beijing Key Laboratory, College of Life Sciences, Beijing Normal University, Beijing, 100875, China.
authors.forename: Xueping
authors.initials: X
authors.lastname: She
authors.affiliation: Gene Engineering and Biotechnology Beijing Key Laboratory, College of Life Sciences, Beijing Normal University, Beijing, 100875, China.
authors.forename: Mengqian
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Gene Engineering and Biotechnology Beijing Key Laboratory, College of Life Sciences, Beijing Normal University, Beijing, 100875, China. yangdong@bnu.edu.cn.
authors.forename: Dong
authors.initials: D
authors.lastname: Yang
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D002176:Candida albicans / Q000201:enzymology* / Q000254:growth & development*; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D017353:Gene Deletion; D006801:Humans; D006863:Hydrogen-Ion Concentration; D025301:Hyphae / Q000254:growth & development*; D020128:Inhibitory Concentration 50; D011799:Quinazolines / Q000378:metabolism*; D037521:Virulence Factors / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; C558357:N2,N4-dibenzylquinazoline-2,4-diamine; D011799:Quinazolines; D037521:Virulence Factors; D000251:Adenosine Triphosphatases; C539750:VPS4 protein, Candida albicans
keywords: Candida albicans; DBeQ; ESCRT; Hyphal; Polarity; Vps4