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bioRxiv · 10.1101/2020.09.29.318048

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

Mamouei, Z.·Singh, S.·Lemire, B.·Gu, Y.·Alqarihi, A.·Nabeela, S.·Li, D.·Ibrahim, A.·Uppuluri, P.
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Abstract

A forward genetic screening approach identified orf19.2500, as a gene controlling Candida albicans biofilm dispersal and biofilm detachment. Three-dimensional (3-D) 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 three 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 of the respiratory electron transport chain, 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.

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Mamouei, Z., Singh, S., Lemire, B., Gu, Y., Alqarihi, A., Nabeela, S., Li, D., Ibrahim, A., Uppuluri, P.. 2020-09-29. An evolutionarily diverged mitochondrial protein controls biofilm growth and virulence in Candida albicans. https://doi.org/10.1101/2020.09.29.318048

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