{"doi":"10.1101/2023.02.23.529756","title":"<i>Candida albicans</i> stimulates the formation of a multi-receptor complex that mediates epithelial cell invasion during oropharyngeal infection","abstract":"Summary Fungal invasion of the oral epithelium is central to the pathogenesis of oropharyngeal candidiasis (OPC). Candida albicans invades the oral epithelium by receptor-induced endocytosis but this process is incompletely understood. We found that C. albicans infection of oral epithelial cells induces c-Met to form a multi-protein complex with E-cadherin and the epidermal growth factor receptor (EGFR). E-cadherin is necessary for C. albicans to activate both c-Met and EGFR and to induce the endocytosis of C. albicans . Proteomics analysis revealed that c-Met interacts with C. albicans Hyr1, Als3 and Ssa1. Both Hyr1 and Als3 were required for C. albicans stimulation of c-Met and EGFR in oral epithelial cells in vitro and for full virulence during OPC in mice. Treating mice with small molecule inhibitors of c-Met and EGFR ameliorated OPC, demonstrating the potential therapeutic efficacy of blocking these host receptors for C. albicans . Graphical abstract Highlights c-Met is an oral epithelial cell receptor for Candida albicans C. albicans infection causes c-Met and the epidermal growth factor receptor (EGFR) to form a complex with E-cadherin, which is required for c-Met and EGFR function C. albicans Hyr1 and Als3 interact with c-Met and EGFR, inducing oral epithelial cell endocytosis and virulence during oropharyngeal candidiasis Dual blockade of c-Met and EGFR ameliorates oropharyngeal candidiasis","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":395869,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9562,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":314446,"name":"Norma V. Solis","orcid":"0000-0001-5163-2110","position":1,"is_corresponding":false},{"id":379052,"name":"Max V. Cravener","orcid":"0000-0002-5591-3304","position":2,"is_corresponding":false},{"id":314447,"name":"Marc Swidergall","orcid":"0000-0002-5261-6267","position":3,"is_corresponding":false},{"id":319876,"name":"Jianfeng Lin","orcid":"0000-0002-5202-6304","position":4,"is_corresponding":false},{"id":329641,"name":"Manning Y. Huang","orcid":"0000-0001-6045-9698","position":5,"is_corresponding":false},{"id":821765,"name":"Hong Liu","orcid":"0000-0003-3491-3476","position":6,"is_corresponding":false},{"id":308238,"name":"Shakti Singh","orcid":"0000-0001-6521-0998","position":7,"is_corresponding":false},{"id":294225,"name":"Ashraf S. Ibrahim","orcid":"0000-0003-3787-8530","position":8,"is_corresponding":false},{"id":842347,"name":"Massimiliano Mazzone","orcid":"0000-0001-8824-4015","position":9,"is_corresponding":false},{"id":329643,"name":"Aaron P. Mitchell","orcid":"0000-0002-0868-4000","position":10,"is_corresponding":false},{"id":294224,"name":"Scott G. Filler","orcid":"0000-0001-7278-3700","position":11,"is_corresponding":false},{"id":587437,"name":"Quynh T. Phan","orcid":null,"position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-19T01:19:27.044553Z","pmid":"36865306","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":[]}