Insights Into the Role of Hog1 Signaling Cascade Sln1-Ssk1-Ssk2-Pbs2 and Sho1 Osmosensor in the Regulation of White-Opaque Switching in Candida albicans
Date Issued
2014
Date
2014
Author(s)
Liang, Shen-Huan
Abstract
Fungal pathogen Candida albicans is prevalent in healthy human populations, widely found in the normal gastrointestinal flora. Severe Systemic infections are commonly found in individuals with a depressed immune system, associated with aging, diseases or therapies. White-opaque switching is an epigenetic morphological change in C. albicans. This phenotypic switch regulates many properties including biofilm formation, virulence and sexual mating. The switching frequency is highly associated with different stresses, such as O2, temperature, CO2, oxidative stress and the growth rate. The osmotic response MAPK gene, HOG1, has been known for helping the cell cope with the osmotic and oxidative stress, although unlike Saccharomyce cerevisiae, Sho1, the osmosensor, does not play a central role in activation of Hog1 in C. albicans. In our previous study, Hog1 MAPK is involved in the regulation of white-opaque switching. Homozygous wild type strains (MTLa/a and MTLα/α) cannot undergo white-opaque switching on synthetic complete (SC) medium, with a switching frequency less than 10-3. Deletion of the HOG1 gene in MTLa/a or MTLα/α strains stimulates switching with a frequency of 100% on SC medium. Nevertheless, this phenomenon is not observed in a/α cells, suggesting that the phenotypic change is also inhibited by the a1/α2 complex. Therefore, in this study, I have further identified the role of four upstream components (Pbs2 MAPKK, Ssk2 MAPKKK, Ssk1 and Sln1) of the Hog1 SAPK pathway, and the osmosensor Sho1, the one that does not mediate Hog1 activation in C. albicans, in white-opaque switching. As expected, deletion of PBS2 and SSK2 in homozygous C. albicans cells induced 100% of phenotypic transition from white to opaque cells. Interestingly, inactivation of the SSK1 gene caused 41 ± 8% of colonies to form opaque cells, suggesting the existence of an alternative pathway regulating the white-opaque switch in the Hog1 MAPK pathway, given that the switching frequencies of ssk1 mutants were much lower than those of ssk2 and pbs2 mutants. On the other hand, homozygous sln1 and sho1 mutants remain white colonies on the SC medium. Western blotting revealed that the Hog1 phosphorylation is positively regulated by the upstream component, Pbs2, Ssk2 and Ssk1, but negatively regulated in both of MTLa/a and MTLa/α of sln1 mutants. Under pheromone treatment, ssk1, ssk2 and pbs2 mutants exhibited shorter mating projections compared to those of the wild-type strain. Surprisingly, the white-to-opaque switching experiment showed that sho1 mutants displayed a lower switching frequency (16.5 ± 3.60%) than those of the wild type (32.7 ± 10.00%) on Lee’s N-acetylglucosamine medium, implicating that an unknown mechanism is involved in this phenotypic change through the Sho1 pathway. Taken together, our study has provided two alternative signaling pathways (Hog1 MAPK and Sho1 osmosensing pathways) involved in this unique phenotypic switch in C. albicans and will elucidate how the interaction happens between the Wor1 and these pathways.
Subjects
白色念珠球菌
White-Opaque 型態轉換
Hog1 訊息傳遞路徑
氧化壓力
Sho1 滲透壓訊息傳導路徑
交配
SDGs
Type
thesis
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