Mooning the immune system: Elucidating the role of the moonlighting protein Gpd2 in the pathogenicity of Candida albicans

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One of the most common yeast infections affecting women's health is genital thrush, which is caused by Candida albicans. Each year, 75% of women will experience an episode of genital thrush, with up to 15% of these women going on to develop recurrent infection which is defined as three or more episodes within a 12-month period. Recent estimates suggest that there are over 138 million cases of recurrent infection each year. Women with high circulatory levels of the hormone oestrogen, that occur naturally during pregnancy, or result from the use of oral contraceptives and hormone replacement therapy are at increased risk of developing genital thrush. Although not life-threatening, these infections are painful, can lead to complications during pregnancy, and have a significant effect on the wellbeing of women. Therefore, understanding why women with higher oestrogen levels are at an increased risk of infection is paramount. The main function of the human immune system is to recognised foreign particles as "non-self" and to remove them from the human body. Key to the clearance of the yeast C. albicans are white blood cells (also known as phagocytes) that engulf and destroy microbes. These white blood cells work together with proteins located in body fluids known as complement. Complement proteins stick to the surface of foreign particles like C. albicans and target them for destruction by the phagocytes. However, during genital thrush there is a breakdown in this immune protection and the innate immune system no longer clears the yeast from the female genital tract.Recently, we have shown that phagocytes are less able to engulf and destroy C. albicans, if the yeast has been exposed to oestrogen. This reduced immune response is due to the increased expression of a yeast protein called Gpd2. This yeast protein functions to bind human proteins which disguise the yeast as "self" and subsequently prevent complement proteins sticking to the yeast cell surface. As a result, the yeast is no longer recognised as "non-self" and is, therefore, not cleared from the body by the innate immune system resulting in infection. Removing this single yeast protein restores the ability of complement proteins to stick to the yeast cell surface and ensures effective removal of the yeast by the phagocytes. Therefore, we now want to know how the level of this protein is increased by the presence of oestrogen, how the protein gets to the yeast cell surface, and the role this protein plays in infection. Addressing these important questions will identify novel yeast targets to which we can design new drugs to, as a way to either prevent or treat infections, and will provide critical information to improve women's health and wellbeing.