Regulation of stress responses in the fungal pathogen 'Candida albicans'
In the model yeast, Saccharomyces cerevisiae, the general stress response is mediated by two partially redundant Cys2His2 zinc finger transcription factors, Msn2 and Msn4. These proteins bind to STress Response Elements (STRE) within the promoter region of target genes. Two genes containing sequence similarity to the S. cerevisiae MSN2/4 zinc finger DNA-binding region were identified in the C. albicans genome (CaMSN4 and MNL1). Complementation experiments showed that CaMSN4 but not MNL1 has weak activity in S. cerevisiae msn2 msn4 cells. Extensive phenotypic analysis and transcript profiling revealed no significant difference between wild type and msn4 mn11 C. albicans cells when placed under a variety of stress conditions. Furthermore, molecular analyses of Msn4 and Mn11 suggested that these putative transcription factors might not be active in C. albicans. CaMsn4 and CaMn11 do not contribute significantly to C. albicans stress responses under any of the conditions tested (heat shock, osmotic and oxidative stress, carbon starvation, and pH). These results indicated that, compared with S. cerevisiae, Msn2/4-like proteins have evolved different roles in C. albicans. This was consistent with a previous transcript profiling study which suggested that C. albicans lacks the general response to stress previously identified in S. cerevisiae and Schizosaccharomyces pombe. However, in S. pombe, the general stress response is mediated by Hogl, not Msn2/4-like proteins. Therefore the role of the Hog1 stress-activated protein kinase (SAPK) pathway in mediating stress responses in C. albicans was characterised. Hog1 is phosphorylated and accumulates in the nucleus in response to a diverse range of stimuli including osmotic stress, high levels of oxidative stress, heavy metal stress and the quorum sensing molecule farnesol. In addition, Hog1-regulated genes that are commonly induced in response to a diverse range of stress conditions were identified.