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

被引:2
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
来源
CELL REPORTS | 2024年 / 43卷 / 08期
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. .
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页数:24
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共 89 条
  • [1] The Gene Ontology knowledgebase in 2023
    Aleksander, Suzi A.
    Balhoff, James
    Carbon, Seth
    Cherry, J. Michael
    Drabkin, Harold J.
    Ebert, Dustin
    Feuermann, Marc
    Gaudet, Pascale
    Harris, Nomi L.
    Hill, David P.
    Lee, Raymond
    Mi, Huaiyu
    Moxon, Sierra
    Mungall, Christopher J.
    Muruganugan, Anushya
    Mushayahama, Tremayne
    Sternberg, Paul W.
    Thomas, Paul D.
    Van Auken, Kimberly
    Ramsey, Jolene
    Siegele, Deborah A.
    Chisholm, Rex L.
    Fey, Petra
    Aspromonte, Maria Cristina
    Nugnes, Maria Victoria
    Quaglia, Federica
    Tosatto, Silvio
    Giglio, Michelle
    Nadendla, Suvarna
    Antonazzo, Giulia
    Attrill, Helen
    dos Santos, Gil
    Marygold, Steven
    Strelets, Victor
    Tabone, Christopher J.
    Thurmond, Jim
    Zhou, Pinglei
    Ahmed, Saadullah H.
    Asanitthong, Praoparn
    Luna Buitrago, Diana
    Erdol, Meltem N.
    Gage, Matthew C.
    Ali Kadhum, Mohamed
    Li, Kan Yan Chloe
    Long, Miao
    Michalak, Aleksandra
    Pesala, Angeline
    Pritazahra, Armalya
    Saverimuttu, Shirin C. C.
    Su, Renzhi
    [J]. GENETICS, 2023, 224 (01)
  • [2] ALTSCHUL SF, 1990, J MOL BIOL, V215, P403, DOI 10.1006/jmbi.1990.9999
  • [3] Adapting to survive: How Candida overcomes host-imposed constraints during human colonization
    Alves, Rosana
    Barata-Antunes, Claudia
    Casal, Margarida
    Brown, Alistair J. P.
    Van Dijck, Patrick
    Paiva, Sandra
    [J]. PLOS PATHOGENS, 2020, 16 (05)
  • [4] Gene Ontology: tool for the unification of biology
    Ashburner, M
    Ball, CA
    Blake, JA
    Botstein, D
    Butler, H
    Cherry, JM
    Davis, AP
    Dolinski, K
    Dwight, SS
    Eppig, JT
    Harris, MA
    Hill, DP
    Issel-Tarver, L
    Kasarskis, A
    Lewis, S
    Matese, JC
    Richardson, JE
    Ringwald, M
    Rubin, GM
    Sherlock, G
    [J]. NATURE GENETICS, 2000, 25 (01) : 25 - 29
  • [5] Transcriptional Regulation of Carbohydrate Metabolism in the Human Pathogen Candida albicans
    Askew, Christopher
    Sellam, Adnane
    Epp, Elias
    Hogues, Herve
    Mullick, Alaka
    Nantel, Andre
    Whiteway, Malcolm
    [J]. PLOS PATHOGENS, 2009, 5 (10)
  • [6] Cell cycle arrest during S or M phase generates polarized growth via distinct signals in Candida albicans
    Bachewich, C
    Nantel, A
    Whiteway, M
    [J]. MOLECULAR MICROBIOLOGY, 2005, 57 (04) : 942 - 959
  • [7] Niche-specific regulation of central metabolic pathways in a fungal pathogen
    Barelle, CJ
    Priest, CL
    MacCallum, DM
    Gow, NAR
    Odds, FC
    Brown, AJP
    [J]. CELLULAR MICROBIOLOGY, 2006, 8 (06) : 961 - 971
  • [8] FungiDB: An Integrated Bioinformatic Resource for Fungi and Oomycetes
    Basenko, Evelina Y.
    Pulman, Jane A.
    Shanmugasundram, Achchuthan
    Harb, Omar S.
    Crouch, Kathryn
    Starns, David
    Warrenfeltz, Susanne
    Aurrecoechea, Cristina
    Stoeckert, Christian J., Jr.
    Kissinger, Jessica C.
    Roos, David S.
    Hertz-Fowler, Christiane
    [J]. JOURNAL OF FUNGI, 2018, 4 (01)
  • [9] UniProt: the universal protein knowledgebase in 2021
    Bateman, Alex
    Martin, Maria-Jesus
    Orchard, Sandra
    Magrane, Michele
    Agivetova, Rahat
    Ahmad, Shadab
    Alpi, Emanuele
    Bowler-Barnett, Emily H.
    Britto, Ramona
    Bursteinas, Borisas
    Bye-A-Jee, Hema
    Coetzee, Ray
    Cukura, Austra
    Da Silva, Alan
    Denny, Paul
    Dogan, Tunca
    Ebenezer, ThankGod
    Fan, Jun
    Castro, Leyla Garcia
    Garmiri, Penelope
    Georghiou, George
    Gonzales, Leonardo
    Hatton-Ellis, Emma
    Hussein, Abdulrahman
    Ignatchenko, Alexandr
    Insana, Giuseppe
    Ishtiaq, Rizwan
    Jokinen, Petteri
    Joshi, Vishal
    Jyothi, Dushyanth
    Lock, Antonia
    Lopez, Rodrigo
    Luciani, Aurelien
    Luo, Jie
    Lussi, Yvonne
    Mac-Dougall, Alistair
    Madeira, Fabio
    Mahmoudy, Mahdi
    Menchi, Manuela
    Mishra, Alok
    Moulang, Katie
    Nightingale, Andrew
    Oliveira, Carla Susana
    Pundir, Sangya
    Qi, Guoying
    Raj, Shriya
    Rice, Daniel
    Lopez, Milagros Rodriguez
    Saidi, Rabie
    Sampson, Joseph
    [J]. NUCLEIC ACIDS RESEARCH, 2021, 49 (D1) : D480 - D489
  • [10] The Karyopherin Kap95 and the C-Termini of Rfa1, Rfa2, and Rfa3 Are Necessary for Efficient Nuclear Import of Functional RPA Complex Proteins in Saccharomyces cerevisiae
    Belanger, Kenneth D.
    Griffith, Amanda L.
    Baker, Heather L.
    Hansen, Jeanne N.
    Kovacs, Laura A. Simmons
    Seconi, Justin S.
    Strine, Andrew C.
    [J]. DNA AND CELL BIOLOGY, 2011, 30 (09) : 641 - 651