Block two proteins to restrain candidiasis

Histologic staining of a kidney infected by Candida; note the filamentous shape of the fungal hyphae. Histologic staining of a kidney infected by Candida; note the filamentous shape of the fungal hyphae. Ana Cuenda y Juan José Sanz. / CNB-CSIC

A lack of p38γ and p38δ increases the efficiency of innate immune cells against systemic Candida albicans infection. This lack also reduces the elevated inflammation behind organ damage. Drugs that inhibit these proteins have potential use as therapy against systemic candidiasis, a condition affecting thousands of people each year worldwide.

Candida albicans is a fungus that is a normal component of the human microbiota. However, excessive growth of this fungus can cause an infection that reaches the bloodstream, giving rise to a severe health condition. Researchers from the Centro Nacional de Biotecnología (CNB-CSIC) in Madrid, Spain, have identified two proteins, p38γ and p38δ, which play an important role in regulating Candida infection.

This paper, published in the journal EMBO Molecular Medicine, uses an animal model of candidiasis to show that the absence of p38γ and p38δ restrains the infection by acting on two levels. A lack of these proteins causes both an increase in the natural antifungal capacity of innate immune cells and a dampening of the acute inflammatory response that can produce severe organ damage.

“Administration of inhibitor drugs against p38γ and p38δ in Candida-infected mice leads to a reduction of the fungal load in key organs such as the kidney,” explains Ana Cuenda, principal investigator of the study. “This suggests that both proteins could be targets for the development of new drugs to treat Candida infection in humans, offering increased specificty and efficiency over those currently available.”

Although fungal infection poses a substantial threat, its impact on human health is given lower priority than other infectious diseases. Each year, systemic candidiasis affects 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 as well as patients undergoing chemotherapy or immunosuppressive treatments due to organ transplantation. In these groups, mortality caused by systemic candidiasis can be as high as 40%.

“Current treatments are insufficient, and resistance to antifungal drugs is on the rise. In recent years, Candida infections have raised significantly. Understanding the role of p38γ and p38δ in Candida infection offers new strategies in the fight against candidiasis,” remarks Cuenda

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