Functional genomic analysis of genes important for Candida albicans fitness in diverse environmental conditions

被引:3
作者
Xiong, Emily H. [1 ]
Zhang, Xiang [2 ]
Yan, Huijuan [3 ]
Ward, Henry N. [2 ,4 ]
Lin, Zhen-Yuan [5 ]
Wong, Cassandra J. [5 ]
Fu, Ci [1 ]
Gingras, Anne-Claude [1 ,5 ]
Noble, Suzanne M. [3 ]
Robbins, Nicole [1 ]
Myers, Chad L. [2 ,4 ]
Cowen, Leah E. [1 ]
机构
[1] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada
[2] Univ Minnesota, Dept Comp Sci & Engn, Minneapolis, MN 55455 USA
[3] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
[4] Univ Minnesota, Bioinformat & Computat Biol Grad Program, Minneapolis, MN 55455 USA
[5] Sinai Hlth, Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada
基金
美国国家卫生研究院; 加拿大自然科学与工程研究理事会; 加拿大健康研究院;
关键词
CANDIDA-ALBICANS; GALLERIA-MELLONELLA; PROTEIN IDENTIFICATION; IN-VIVO; SEQUENCE; MODEL; YEAST; ALIGNMENT; SEARCH; HOST;
D O I
10.1016/j.celrep.2024.114601
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Fungal pathogens such as Candida albicans pose a significant threat to human health with limited treatment options available. One strategy to expand the therapeutic target space is to identify genes important for pathogen growth in host-relevant environments. Here, we leverage a pooled functional genomic screening strategy to identify genes important for fitness of C. albicans in diverse conditions. We identify an essential gene with no known Saccharomyces cerevisiae homolog, C1_09670C, , and demonstrate that it encodes subunit 3 of replication factor A (Rfa3). Furthermore, we apply computational analyses to identify functionally coherent gene clusters and predict gene function. . Through this approach, we predict the cell-cycle-associated function of C3_06880W, , a previously uncharacterized gene required for fitness specifically at elevated temperatures, and follow-up assays confirm that C3_06880W encodes Iml3, a component of the C. albicans kinetochore with roles in virulence in vivo. . Overall, this work reveals insights into the vulnerabilities of C. albicans. .
引用
收藏
页数:24
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