دورية أكاديمية
أعرض في EDS

The putative prenyltransferase Nus1 is required for filamentation in the human fungal pathogen Candida albicans.

التفاصيل البيبلوغرافية
العنوان: The putative prenyltransferase Nus1 is required for filamentation in the human fungal pathogen Candida albicans.
المؤلفون: Farheen A; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1M1, Canada., Case NT; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1M1, Canada., MacAlpine J; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1M1, Canada., Fu C; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1M1, Canada., Robbins N; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1M1, Canada., Cowen LE; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1M1, Canada.
المصدر: G3 (Bethesda, Md.) [G3 (Bethesda)] 2024 Aug 07; Vol. 14 (8).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 101566598 Publication Model: Print Cited Medium: Internet ISSN: 2160-1836 (Electronic) Linking ISSN: 21601836 NLM ISO Abbreviation: G3 (Bethesda) Subsets: MEDLINE
أسماء مطبوعة: Publication: 2021- : [Oxford] : Oxford University Press
Original Publication: Bethesda, MD : Genetics Society of America, 2011-
مواضيع طبية MeSH: Candida albicans*/genetics , Candida albicans*/pathogenicity , Fungal Proteins*/genetics , Fungal Proteins*/metabolism, Humans ; Dimethylallyltranstransferase/genetics ; Dimethylallyltranstransferase/metabolism ; Hyphae/growth & development
مستخلص: Candida albicans is a major fungal pathogen of humans that can cause serious systemic infections in vulnerable immunocompromised populations. One of its virulence attributes is its capacity to transition between yeast and filamentous morphologies, but our understanding of this process remains incomplete. Here, we analyzed data from a functional genomic screen performed with the C. albicans Gene Replacement And Conditional Expression collection to identify genes crucial for morphogenesis in host-relevant conditions. Through manual scoring of microscopy images coupled with analysis of each image using a deep learning-based method termed Candescence, we identified 307 genes important for filamentation in tissue culture medium at 37°C with 5% CO2. One such factor was orf19.5963, which is predicted to encode the prenyltransferase Nus1 based on sequence homology to Saccharomyces cerevisiae. We further showed that Nus1 and its predicted interacting partner Rer2 are important for filamentation in multiple liquid filament-inducing conditions as well as for wrinkly colony formation on solid agar. Finally, we highlight that Nus1 and Rer2 likely govern C. albicans morphogenesis due to their importance in intracellular trafficking, as well as maintaining lipid homeostasis. Overall, this work identifies Nus1 and Rer2 as important regulators of C. albicans filamentation and highlights the power of functional genomic screens in advancing our understanding of gene function in human fungal pathogens.
Competing Interests: Conflicts of interest LEC is co-founder and shareholder in Bright Angel Therapeutics, a platform company for the development of novel antifungal therapeutics. LEC is a Science Advisor for Kapoose Creek, a company that harnesses the therapeutic potential of fungi. All other authors declare no competing interests.
(© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)
References: Lancet Infect Dis. 2024 Jul;24(7):e428-e438. (PMID: 38224705)
Open Forum Infect Dis. 2019 Mar 15;6(Suppl 1):S79-S94. (PMID: 30895218)
PLoS One. 2012;7(9):e45912. (PMID: 23049891)
Pathogens. 2021 Jul 07;10(7):. (PMID: 34358008)
Cell Rep. 2018 May 22;23(8):2292-2298. (PMID: 29791841)
Genetics. 2022 Nov 30;222(4):. (PMID: 36226807)
mBio. 2020 Apr 21;11(2):. (PMID: 32317319)
J Lipid Res. 2014 Jul;55(7):1465-77. (PMID: 24868093)
Genetics. 2021 Oct 2;219(2):. (PMID: 34143207)
mBio. 2020 May 5;11(3):. (PMID: 32371596)
J Fungi (Basel). 2020 Feb 24;6(1):. (PMID: 32102426)
Biochim Biophys Acta. 1999 Jan 6;1426(2):297-307. (PMID: 9878797)
PLoS Pathog. 2007 Jun;3(6):e92. (PMID: 17604452)
Yale J Biol Med. 2019 Sep 20;92(3):435-452. (PMID: 31543707)
iScience. 2022 May 18;25(6):104432. (PMID: 35663022)
Microbiol Mol Biol Rev. 2011 Jun;75(2):213-67. (PMID: 21646428)
Sci Transl Med. 2012 Dec 19;4(165):165rv13. (PMID: 23253612)
Nat Commun. 2015 Mar 31;6:6741. (PMID: 25824284)
Mol Biol Cell. 2008 Jan;19(1):284-96. (PMID: 17989363)
Nat Rev Microbiol. 2017 Feb;15(2):96-108. (PMID: 27867199)
J Fungi (Basel). 2020 Jan 17;6(1):. (PMID: 31963458)
Drug Discov Today. 2009 Feb;14(3-4):214-22. (PMID: 19152839)
Microbiol Spectr. 2022 Oct 26;10(5):e0147222. (PMID: 35972285)
Nat Commun. 2021 Nov 11;12(1):6497. (PMID: 34764269)
Nucleic Acids Res. 2017 Jan 4;45(D1):D592-D596. (PMID: 27738138)
FEMS Yeast Res. 2002 Aug;2(3):259-65. (PMID: 12702274)
Mol Microbiol. 2003 Oct;50(1):167-81. (PMID: 14507372)
Mol Cell Biol. 1999 Jan;19(1):471-83. (PMID: 9858571)
mBio. 2023 Dec 19;14(6):e0274523. (PMID: 38038475)
iScience. 2023 Feb 04;26(3):106145. (PMID: 36879823)
Nat Genet. 2010 Jul;42(7):590-8. (PMID: 20543849)
Fungal Genet Biol. 2014 Aug;69:1-12. (PMID: 24875421)
G3 (Bethesda). 2017 Nov 6;7(11):3797-3808. (PMID: 28951491)
معلومات مُعتمدة: R01AI127375 U.S. National Institutes of Health; R01 AI127375 United States AI NIAID NIH HHS; CIHR; FDN-154288 CIHR Foundation; Canada Graduate Scholarships Doctoral Awards; Canadian Institutes for Health Research
فهرسة مساهمة: Keywords: Candida albicans; Rer2; filamentation; fungal pathogen; lipid homeostasis
المشرفين على المادة: 0 (Fungal Proteins)
EC 2.5.1.1 (Dimethylallyltranstransferase)
تواريخ الأحداث: Date Created: 20240614 Date Completed: 20240807 Latest Revision: 20240809
رمز التحديث: 20240809
مُعرف محوري في PubMed: PMC11304969
DOI: 10.1093/g3journal/jkae124
PMID: 38874344
قاعدة البيانات: MEDLINE
الوصف
تدمد:2160-1836
DOI:10.1093/g3journal/jkae124