{"doi":"10.1371/journal.pbio.3000957","title":"An evolutionarily diverged mitochondrial protein controls biofilm growth and virulence in Candida albicans","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.","journal":"PLoS Biology","year":2021,"id":187703,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9525,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":308238,"name":"Shakti Singh","orcid":"0000-0001-6521-0998","position":1,"is_corresponding":false},{"id":747351,"name":"Bernard D. Lemire","orcid":"0000-0002-1512-9064","position":2,"is_corresponding":false},{"id":447320,"name":"Yiyou Gu","orcid":"0000-0002-8295-7222","position":3,"is_corresponding":false},{"id":294222,"name":"Abdullah Alqarihi","orcid":"0000-0003-4408-6398","position":4,"is_corresponding":false},{"id":747352,"name":"Sunna Nabeela","orcid":"0000-0002-8066-2199","position":5,"is_corresponding":false},{"id":484318,"name":"Dongmei Li","orcid":"0000-0002-3272-2513","position":6,"is_corresponding":false},{"id":294225,"name":"Ashraf S. Ibrahim","orcid":"0000-0003-3787-8530","position":7,"is_corresponding":false},{"id":361370,"name":"Priya Uppuluri","orcid":"0000-0002-5889-054X","position":8,"is_corresponding":false},{"id":514415,"name":"Zeinab Mamouei","orcid":"0000-0003-2898-1544","position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-07-18T23:48:55.420619Z","pmid":"33720927","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}