Abstract
Candida albicans is the most important opportunistic fungal pathogen of humans. It is a harmless commensal in a healthy person, but can cause life-threatening invasive infections particularly in immunocompromised patients. C. albicans can adhere to the mucosal surfaces and even to the surfaces of medical devices. Cell adhesion is the first step in C. albicans infection of epithelia. In this study, we found that C. albicans Hom6p has a homoserine dehydrogenase activity and is probably involved in the pathway for threonine and methionine biosynthesis. In polysome profile analysis, deletion of HOM6 caused translational arrest in the absence of amino acid supplements. In addition, we found that C. albican Hom6p has an effect on cell adhesion, which is important for C. albicans virulence. Many cell wall proteins are known to play major roles in cell adhesion; we also demonstrate that Hom6p can localize at cell wall by western blot. Moreover, C. albicans Hom6p affects expression of the cell wall protein Xog1p which is a major exoglucanase and is found to be involved in cell adhesion. Xog1p level increased on the cell wall, however, the overall exoglucanase activity reduced in the hom6hom6 mutant. We speculated that the defect of protein synthesis attenuated expression of other exoglucanases or glucan synthesis-related proteins, and then induced release of Xog1p to the cell wall. C. albicans Hom6p thus had an effect on cell survival and cell adhesion by maintaining protein synthesis and cell wall function. Moreover, this study suggests that Hom6p would be a good target to develop new antifungal drugs. In addition to adhesion, the second part of this work was to study a transcription factor ZCF29 probably involved in stress response in C. albicans. The zcf29zcf29 mutants were sensitive to menadione and caffeine but resistant to fenpropimorph. The transcriptional activity of Zcf29p was induced after menadione treatment, revealed by one-hybrid assay. However, the gene expression and activity of antioxidative enzymes had no differences between wild type and the zcf29zcf29 mutant. In addition, the expression of ERG2, ERG24 and ERG11 genes and the ergosterol content had no differences between wild type and the mutant. Therefore, Zcf29p regulates stress response probably through its control of other genes not tested in our study.