Candida albicansrvs161Δ and rvs167Δ Endocytosis Mutants Are Defective in Invasion into the Oral Cavity

摘要

Invasive growth in tissues by the human fungal pathogen Candida albicans is promoted by a switch from budding to hyphal morphogenesis that is stimulated by multiple environmental factors that can vary at different sites of infection. To identify genes that promote invasive growth in the oral cavity to cause oropharyngeal candidiasis (OPC), we first identified C. albicans mutants that failed to invade agar medium. Analysis of nine severely defective mutants in a mouse model of OPC revealed that the strongest defects were seen for the rvs161 Δ and rvs167 Δ mutants, which lack amphiphysin proteins needed for endocytosis. The rvs Δ mutants initially adhered to the tongue but failed to invade efficiently and were lost from the oral cavity. Previous studies indicated that rvs Δ mutants formed filamentous hyphae in the kidney albeit with morphological abnormalities, suggesting that the rvs Δ mutants were influenced by factors that vary at different sites of infection. Consistent with this, increasing concentrations of CO_(2), an inducer of hyphal growth that is more abundant in internal organs than air, partially rescued the invasive-growth defects of the rvs Δ mutants in vitro . Interestingly, preinduction of the rvs Δ mutants to form hyphae prior to into the oral cavity restored their ability to cause OPC, identifying a key role for endocytosis in initiating invasive hyphal growth. These results highlight the influence of distinct environmental factors in promoting invasive hyphal growth in the oral cavity and indicate that blocking endocytosis could have therapeutic value in preventing the initiation of OPC.