UNLABELLED

Fungal invasion of the oral epithelium is central to the pathogenesis of oropharyngeal candidiasis (OPC). invades the oral epithelium by receptor-induced endocytosis but this process is incompletely understood. We found that 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 to activate both c-Met and EGFR and to induce the endocytosis of . Proteomics analysis revealed that c-Met interacts with Hyr1, Als3 and Ssa1. Both Hyr1 and Als3 were required for 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 .

HIGHLIGHTS

c-Met is an oral epithelial cell receptor for 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 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.