THE DIFFERENTIAL EXPRESSION OF CELL WALL PROTEINS IN THE HUMAN FUNGAL PATHOGEN CANDIDA ALBICANS
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Date
2018-04-23
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Johns Hopkins University
Abstract
Candida albicans is a prevalent opportunistic fungal pathogen which can cause serious diseases from deep mucosal infections to fatal systemic infection. The cell wall of C. albicans is the initial point of interaction with the host during infection and it has an internal polysaccharide layer and an external protein layer. The cell wall proteins are mainly attached to the external layer through GPI anchors and have various functions in nutrient capture, virulence and adhesion. Additionally, the cell wall has three copper-only superoxide dismutases (SOD) SOD4, SOD5 and SOD6 that can protect the yeast from oxidative damage. The rationale for why C. albicans has three unique extracellular SOD enzymes was unknown. Our hypothesis is that each extracellular SOD is expressed under unique environmental conditions, allowing the fungus to survive in many different host niches. To begin to test this hypothesis, we analyzed the expression of the three SODs in comparison to 42 other cell wall proteins by qRT-PCR under four stress conditions differing in metal (iron and copper) content, glucose content and cell morphologies. We found that SOD5 is upregulated in the hyphal morphogenetic state together with some hyphal-induced genes involved in cell adhesion and iron uptake (RBT5, HWP1, ALS3, and HYR1). SOD4 is specifically induced during iron starvation with heme-uptake genes RBT5 and CSA1. The expression of SOD6 is unique and only expressed in yeast-form cells and under iron replete conditions; SOD6 is co-expressed with the adhesion molecule RHD3. The only common pattern with the three SODs is their induction by glucose starvation together with cell wall remodeling genes. In copper starvation, the expression of SODs does not change, although we observe for the first time the induction of heme-uptake genes RBT5, CSA1 and PGA10 with low copper. Overall the three extracellular SODs are induced under very different conditions. Each SOD may be expressed under distinct conditions to protect crucial cell wall proteins from oxidative damage and help C. albicans adapt to different environments in the host.
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C. albicans, cell wall proteins