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

• Main Authors: Zeinab Mamouei, Shakti Singh, Bernard Lemire, Yiyou Gu, Abdullah Alqarihi, Sunna Nabeela, Dongmei Li, Ashraf Ibrahim, Priya Uppuluri
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2021-03-01
• Series: PLoS Biology
• Online Access: https://doi.org/10.1371/journal.pbio.3000957
• ISSN: 1544-9173; 1545-7885

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.