Studie van het celdoodproces in candida albicans

Histatin 5 is an antimicrobial peptide with potent candidacidal activity present in the saliva of humans. Identification of functions involved in histatin 5-induced cell death can help to resolve the mechanism of action of histatin 5. In order to develop novel antifungal compounds, functions involved in this cell death process can be used as targets. By screening an overexpression library and profiling transcription, we identified functions involved in histatin 5-induced cell death in C. albicans. Overexpression analysis of some of these genes demonstrated their influence on cell death. Four of them are related to mitochondrial respiration or oxidative stress (POR1, CAT2, PGA3, TRX1), two are involved in nutrient sensing (GPR1, SNF31), one has an unknown function (IPF2973), one is involved in stress response (DDR48). The succeptibility of Saccharomyces cerevisiae to the antimicrobial peptide, histatin 5, was tested after pre-growth in fermentable and non-fermentable carbon sources and in the absence or presence of the uncoupler of oxidative phosphorylation CCCP. S. cerevisiae was more resistant to histatin 5 when grown on a fermentable carbon source compared to growth on a non-fermentable carbon source, indicating an important role for oxidative phosphorylation in histatin 5-induced cell death. Oxidative phosphorylation is a prerequisite for histatin 5-induced cell death in Candida albicans, this is not the case in S. cerevisiae. Incubation of CCCP-treated S. cerevisiae cells with histatin 5 still resulted in cell death. These results suggest that histatin 5-induced cell death in S. cerevisiae differs from that in C. albicans. Bax is a pro-apoptotic protein involved in the regulation of genetically programmed cell death in mammalian cells. It has been shown that heterologous expression of Bax in several yeast species also induces cell death. We investigated the effects of Bax expression in the yeast Candida albicans. Expression of BAX resulted in growth inhibition and cell death. By fusing Bax with yeGFP, the cell death-inducing effect of Bax was increased. Using this fusion protein we showed that in C. albicans Bax co-localizes with the mitochondria. Furthermore, we showed that expression of Bax in yeast causes the mitochondria to cluster in the perinuclear region.

Author dc:creator

• De Smet, K

Contributors dc:contributor

• Contreras, R

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

und

Identifier

https://biblio.ugent.be/publication/470365
http://doi.org/1854/5922
https://biblio.ugent.be/publication/470365/file/1878675

OAI identifier oai:identifier

oai:archive.ugent.be:470365