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Candida albicans stimulates formation of a multi-receptor complex that mediates epithelial cell invasion during oropharyngeal infection

Year: 2023
Type: article
Abstract: 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 are required for C. albicans to stimulate 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 ameliorates OPC, demonstrating the potential therapeutic efficacy of blocking these host receptors for C. albicans.
DOI: 10.1371/journal.ppat.1011579
Authors: Quynh T. Phan, Norma V. Solis, Max V. Cravener, Marc Swidergall, Jianfeng Lin, Manning Y. Huang, Hong Liu, Shakti Singh, Ashraf S. Ibrahim, Massimiliano Mazzone, Aaron P. Mitchell, Scott G. Filler
Institutions: University of California, Los Angeles, The Lundquist Institute, Harbor–UCLA Medical Center, University of Georgia, University of California, San Francisco, VIB-KU Leuven Center for Cancer Biology, KU Leuven
Language: English
Field: Medicine
Open Access status: gold
Estimated APC paid: $2,655
OpenAlex ID: W4386086248
FWCI: 4.864
Cites: 55
Cited by: 27
Related to: 10