The roles of candida albicans Gpm1p and Tef1p in immune evasion and tissue invasion of the human host

Lopez, Crisanto Maglaque

Candida albicans is an opportunistic pathogenic fungus which causes infections in humans. Proteins of C. albicans interact with host immune complement proteins and adhere to host cells. However, deletions of genes expressing identified proteins do not totally abolish the interactions of C. albicans with the corresponding ligands. Thus, there are other C. albicans proteins which mediate these interactions. It was therefore aimed to identify the roles of surface phospholgyerate mutase (Gpm1p) and translation elongation factor 1-alpha (Tef1p) of C. albicans in the immune evasion and tissue invasion of the human host. C. albicans Gpm1p binds the surface of human umbilical vein endothelial cells and keratinocytes by using the host vitronectin as ligand. gpm1 null mutant fails to adhere to, while the Gpm1p-coated latex beads readily associated with, endothelial cells. Moreover, Gpm1p colocalizes with the surface vitronectin of human cells. Gpm1p binds to heparin binding sites of vitronectin. C. albicans Tef1p mediates fungal interaction with human complement regulator plasminogen. Tef1p-bound plasminogen is activated to plasmin and maintains degradation activity on the opsonin C3b. TEF1 is not an essential gene in C. albicans as the tef1 null mutant has the same phenotype as the wild type strain in terms of growth rate and resistance to various stressors. But, the tef1 null mutant binds less plasminogen as compared to the wild type. Moreover, Tef1p binds to neutrophils and tef1 null mutant decreases reactive oxygen species production by neutrophils. Taken together, this dissertation demonstrates the Gpm1p and Tef1p are cell surface proteins of C. albicans relevant to the virulence of the pathogen, both for human immune evasion and host tissue adherence. Elucidating the mechanisms how C. albicans uses its surface proteins can give light to possible strategies to combat this menacing fungal pathogen.

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Lopez, Crisanto Maglaque: The roles of candida albicans Gpm1p and Tef1p in immune evasion and tissue invasion of the human host. 2013.

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