An evolutionarily diverged mitochondrial protein controls biofilm growth and virulence in Candida albicans.
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 functiona...
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2021-03-01
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doaj-f054ab564a1247af874f873588acd5fe2021-07-29T04:34:18ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852021-03-01193e300095710.1371/journal.pbio.3000957An evolutionarily diverged mitochondrial protein controls biofilm growth and virulence in Candida albicans.Zeinab MamoueiShakti SinghBernard LemireYiyou GuAbdullah AlqarihiSunna NabeelaDongmei LiAshraf IbrahimPriya UppuluriA 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.https://doi.org/10.1371/journal.pbio.3000957 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zeinab Mamouei Shakti Singh Bernard Lemire Yiyou Gu Abdullah Alqarihi Sunna Nabeela Dongmei Li Ashraf Ibrahim Priya Uppuluri |
spellingShingle |
Zeinab Mamouei Shakti Singh Bernard Lemire Yiyou Gu Abdullah Alqarihi Sunna Nabeela Dongmei Li Ashraf Ibrahim Priya Uppuluri An evolutionarily diverged mitochondrial protein controls biofilm growth and virulence in Candida albicans. PLoS Biology |
author_facet |
Zeinab Mamouei Shakti Singh Bernard Lemire Yiyou Gu Abdullah Alqarihi Sunna Nabeela Dongmei Li Ashraf Ibrahim Priya Uppuluri |
author_sort |
Zeinab Mamouei |
title |
An evolutionarily diverged mitochondrial protein controls biofilm growth and virulence in Candida albicans. |
title_short |
An evolutionarily diverged mitochondrial protein controls biofilm growth and virulence in Candida albicans. |
title_full |
An evolutionarily diverged mitochondrial protein controls biofilm growth and virulence in Candida albicans. |
title_fullStr |
An evolutionarily diverged mitochondrial protein controls biofilm growth and virulence in Candida albicans. |
title_full_unstemmed |
An evolutionarily diverged mitochondrial protein controls biofilm growth and virulence in Candida albicans. |
title_sort |
evolutionarily diverged mitochondrial protein controls biofilm growth and virulence in candida albicans. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Biology |
issn |
1544-9173 1545-7885 |
publishDate |
2021-03-01 |
description |
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. |
url |
https://doi.org/10.1371/journal.pbio.3000957 |
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