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一种进化上分化的线粒体蛋白控制白色念珠菌生物膜生长和毒力。

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

机构信息

David Geffen School of Medicine, University of California (UCLA), Los Angeles, California, United States of America.

Division of Infectious Disease, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California, United States of America.

出版信息

PLoS Biol. 2021 Mar 15;19(3):e3000957. doi: 10.1371/journal.pbio.3000957. eCollection 2021 Mar.

DOI:10.1371/journal.pbio.3000957
PMID:33720927
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8007014/
Abstract

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.

摘要

正向遗传筛选方法确定 orf19.2500 为控制白色念珠菌生物膜分散和生物膜脱落的基因。三维（3D）蛋白质建模和生物信息学表明，orf19.2500 是一种保守的线粒体蛋白，结构上与角鲨烯/植物烯合酶家族相似，但功能上有所不同。白色念珠菌 orf19.2500 有 3 个进化获得的氨基酸插入片段，除了少数子囊菌真菌外，在所有其他真核生物中都不存在。生化分析表明，orf19.2500 是呼吸电子传递链（ETC）中 NADH 泛醌氧化还原酶复合物 I（CI）组装和活性所必需的，因此被命名为 NDU1。NDU1 对于呼吸和替代碳源的生长是必需的，对于免疫逃避很重要，对于血液传播念珠菌病的小鼠模型中的毒力是必需的，并且可以增强对抗真菌药物的耐药性。我们的研究首次报道了一种蛋白质，它仅基于新氨基酸插入的进化“获得”，将类似于念珠菌的真菌与所有其他真核生物在系统发育上区分开来，而这些插入也是蛋白质的功能中心。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/632e/8007014/9cdf15b33130/pbio.3000957.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/632e/8007014/1aabfd622558/pbio.3000957.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/632e/8007014/110b669b99a6/pbio.3000957.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/632e/8007014/72c7e460732e/pbio.3000957.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/632e/8007014/95310a56ba11/pbio.3000957.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/632e/8007014/04a0de34245a/pbio.3000957.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/632e/8007014/36f7d08d2a87/pbio.3000957.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/632e/8007014/9cdf15b33130/pbio.3000957.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/632e/8007014/1aabfd622558/pbio.3000957.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/632e/8007014/110b669b99a6/pbio.3000957.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/632e/8007014/72c7e460732e/pbio.3000957.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/632e/8007014/95310a56ba11/pbio.3000957.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/632e/8007014/04a0de34245a/pbio.3000957.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/632e/8007014/36f7d08d2a87/pbio.3000957.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/632e/8007014/9cdf15b33130/pbio.3000957.g007.jpg

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