An evolutionarily diverged mitochondrial protein controls biofilm growth and virulence in Candida albicans

被引：10

作者：

Mamouei, Zeinab ^{[1
]}

Singh, Shakti ^{[2
]}

Lemire, Bernard ^{[3
]}

Gu, Yiyou ^{[2
]}

Alqarihi, Abdullah ^{[2
]}

Nabeela, Sunna ^{[2
]}

Li, Dongmei ^{[4
]}

Ibrahim, Ashraf ^{[1
,2
]}

Uppuluri, Priya ^{[1
,2
]}

机构：

[1] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA

[2] Harbor UCLA Med Ctr, Lundquist Inst Biomed Innovat, Div Infect Dis, Torrance, CA 90509 USA

[3] Univ Alberta, Dept Biochem, Edmonton, AB, Canada

[4] Georgetown Univ, Med Ctr, Dept Microbiol & Immunol, Washington, DC 20007 USA

来源：

PLOS BIOLOGY | 2021年 / 19卷 / 03期

关键词：

D O I：

10.1371/journal.pbio.3000957

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A forward genetic screening approach identified orf19.2500 as a gene controlling Candida albicans biofilm dispersal and biofilm detachment. Three-dimensional (3D) protein modeling and bioinformatics revealed that orf19.2500 is a conserved mitochondrial protein, structurally similar to, but functionally diverged from, the squalene/phytoene synthases family. The C. albicans orf19.2500 is distinguished by 3 evolutionarily acquired stretches of amino acid inserts, absent from all other eukaryotes except a small number of ascomycete fungi. Biochemical assays showed that orf19.2500 is required for the assembly and activity of the NADH ubiquinone oxidoreductase Complex I (CI) of the respiratory electron transport chain (ETC) and was thereby named NDU1. NDU1 is essential for respiration and growth on alternative carbon sources, important for immune evasion, required for virulence in a mouse model of hematogenously disseminated candidiasis, and for potentiating resistance to antifungal drugs. Our study is the first report on a protein that sets the Candida-like fungi phylogenetically apart from all other eukaryotes, based solely on evolutionary "gain" of new amino acid inserts that are also the functional hub of the protein.

引用

页数：27