Project description:Two-component signal transduction pathways are one of the primary means by which microorganisms respond to environmental signals. These signaling cascades originated in prokaryotes and were inherited by eukaryotes via endosymbiotic lateral gene transfer from ancestral cyanobacteria. We report here that the nuclear genome of pathogenic fungus Candida albicans contains elements of a two-component signaling pathway that seem to be targeted to the mitochondria. In C. albicans two-component response regulator protein Srr1(Stress Response Regulator) contains a mitochondrial targeting sequence at the N-terminus, and fluorescence microscopy reveals mitochondrial localization of GFP-tagged Srr1p. Moreover, phylogenetic analysis indicates that C. albicans Srr1p is more closely related to histidine kinases and response regulators found in marine bacteria compared to other two-component proteins present in the fungi. These data suggest conservation of this protein during the evolutionary transition from endosymbiont to a subcellular organelle. We used microarray analysis to determine if the phenotypes observed with srr1M-NM-^T/M-NM-^T mutant could be correlated with gene transcriptional changes. Expression of mitochondrial genes was altered in the srr1M-NM-^T/M-NM-^T null mutant in comparison to the wild type. Furthermore, apoptosis significantly increased in the srr1M-NM-^T/M-NM-^T mutant strain compared to wild type, suggesting activation of mitochondria dependent apoptotic cell death pathway in the srr1M-NM-^T/M-NM-^T mutant. This study shows for the first time that a lower eukaryote like C. albicans possesses a two-component response regulator protein that has survived in mitochondria and regulates a subset of genes whose functions are associated with oxidative stress response and programmed cell death (apoptosis). Candida albicans wildtype or srr1 null cells were left untreated or were treated with either 8mM H2O2 for one hour prior to RNA isolation.
Project description:Two-component signal transduction pathways are one of the primary means by which microorganisms respond to environmental signals. These signaling cascades originated in prokaryotes and were inherited by eukaryotes via endosymbiotic lateral gene transfer from ancestral cyanobacteria. We report here that the nuclear genome of pathogenic fungus Candida albicans contains elements of a two-component signaling pathway that seem to be targeted to the mitochondria. In C. albicans two-component response regulator protein Srr1(Stress Response Regulator) contains a mitochondrial targeting sequence at the N-terminus, and fluorescence microscopy reveals mitochondrial localization of GFP-tagged Srr1p. Moreover, phylogenetic analysis indicates that C. albicans Srr1p is more closely related to histidine kinases and response regulators found in marine bacteria compared to other two-component proteins present in the fungi. These data suggest conservation of this protein during the evolutionary transition from endosymbiont to a subcellular organelle. We used microarray analysis to determine if the phenotypes observed with srr1Δ/Δ mutant could be correlated with gene transcriptional changes. Expression of mitochondrial genes was altered in the srr1Δ/Δ null mutant in comparison to the wild type. Furthermore, apoptosis significantly increased in the srr1Δ/Δ mutant strain compared to wild type, suggesting activation of mitochondria dependent apoptotic cell death pathway in the srr1Δ/Δ mutant. This study shows for the first time that a lower eukaryote like C. albicans possesses a two-component response regulator protein that has survived in mitochondria and regulates a subset of genes whose functions are associated with oxidative stress response and programmed cell death (apoptosis).
Project description:The opportunistic human pathogens, Candida albicans and Candida dubliniensis, are closely related species displaying large differences in virulence, but the reasons for these differences are elusive. Microarray-based comparative analysis of global gene expression in the two species incubated on reconstituted human oral epithelium (RHE) was used to identify specific and common changes in gene expression and find novel C. albicans virulence genes
Project description:Purpose: To explore the influence of Candida albicans treatment in mice intestinal epithelia. Method: 108 CFU C. albicans or PBS was gavaged to Apoe-/- mice every 3 days for 2 weeks. mRNA profiles were generated by deep sequencing.Results: Several signaling pathways were changed after C. albicans treatment, including response to hypoxia pathway.