An evolutionarily diverged mitochondrial protein controls biofilm growth and virulence in Candida albicans.
| Autor: | Zeinab Mamouei, Shakti Singh, Bernard Lemire, Yiyou Gu, Abdullah Alqarihi, Sunna Nabeela, Dongmei Li, Ashraf Ibrahim, Priya Uppuluri |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | PLoS Biology, Vol 19, Iss 3, p e3000957 (2021) |
| Druh dokumentu: | article |
| ISSN: | 1544-9173 1545-7885 |
| DOI: | 10.1371/journal.pbio.3000957 |
| Popis: | 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. |
| Databáze: | Directory of Open Access Journals |
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