抄録
The human pathogenic fungus Candida albicans can cause a wide range of infections including oral thrush and life threatening systemic candidosis. However, the mechanisms by which C. albicans invades and persists within mucosal epithelium or organs such as the liver are not clear. We characterized the cellular and molecular mechanisms of epithelial-fungus interactions and liver invasion using reconstituted human oral epithelium (RHE), infected organs from animals and clinical samples. We observed that hyphal formation facilitates epithelial invasion via both active (physical penetration) and passive (induced endocytosis) processes. To identify C. albicans genes that are expressed during invasion of epithelial cells and liver tissue, we used genome-wide transcriptional profiling in vivo and ex vivo. By analysing the different phases of infection from attachment to tissue penetration in a time course experiment and in patient samples, and by comparing the profiles of an invasive with those of a non-invasive strain, we identified genes and transcriptional patterns which are associated with the invasion process. This includes genes involved in metabolism, stress, nutrient uptake, as well as transcriptional programmes regulating morphology and environmental sensing. We identified several novel infection-associated genes with unknown function. One gene, up regulated in both RHE infection and patients, named EED1, was essential for maintenance of hyphal elongation. Mutants lacking EED1 showed transient cell elongation on epithelial tissue, which enabled only superficial invasion of epithelial cells. Once inside an epithelial cell, Δeed1 cells could proliferate as yeasts or pseudohyphae but remained trapped intracellularly. Our results suggest that the adaptive response and morphology of C. albicans play specific roles for host-fungal interactions during mucosal and systemic infections.
