Candida albicans is a fungus that is a normal component of the human microbiota. However, sometimes it overgrowths and can cause an infection that reaches the bloodstream, generating a severe health problem. Researchers from the Centro Nacional de Biotecnología (CNB-CSIC) in Madrid, Spain, have identified two proteins, p38γ and p38δ, which have an important role in regulating Candida infection.

This work, published in EMBO Molecular Medicine, shows that in an animal model of candidiasis the absence of p38γ and p38δ restrains the infection, acting at two levels. Lack of these proteins increases the natural antifungal capacity of innate immune cells. At the same time, the acute inflammatory response that can produce a severe damage in the organs is dampened.

“Administration of inhibitor drugs against p38γ and p38δ to Candida infected mice leads to a reduction of the fungal load in key organs, such as the kidney -explains Ana Cuenda, principal investigator of this work-. This result suggests that both proteins could be targets for the development of new drugs, more specific and efficient than the currently available, to treat Candida infection in humans”.

Although fungal infection is an important threat, its impact on human health is not as appreciated as other infectious diseases. Systemic candidiasis affects each year more than half a million people around the world. It is a particularly serious problem in immunodeficient patients, such as those suffering from autoimmune diseases or AIDS, or those patients undergoing chemotherapy or immunosuppressive treatments in organ transplantation. In these groups, mortality caused by systemic candidiasis goes up to 40%.

“Current treatments are insufficient and resistance to antifungal drugs is increasing. In the past years Candida infections have raised significantly. Understanding the role of p38γ and p38δ in Candida infection offers new strategies for fighting against candidiasis”, Cuenda says.

Image: Histological staining of a kidney infected by candida; note the fungus hyphae in the form of filaments. Ana Cuenda y Juan José Sanz. / CNB-CSIC

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