Study identifies blood protein albumin as key defense against deadly fungal infection “mucormycosis”

A new international study published in Nature has identified albumin, the most abundant protein in human blood, as a powerful and previously unrecognized defense against mucormycosis, a rare but often fatal fungal infection. The research was led by George Chamilos, MD and his laboratory at the University of Crete and Institute of Molecular Biology and Biotechnology, with critical contributions from a Lundquist Institute for Biomedical Innovation team lead by Professor Ashraf Ibrahim, PhD.

Mucormycosis, sometimes called “black fungus,” is a fast-moving infection caused by Mucorales fungi and can be deadly in up to half of affected patients, and in some cases diagnosis of mucormycosis carries a prognosis of a certain death. The disease surged in India during the COVID-19 pandemic, particularly among individuals with diabetes, weakened immune systems, or malnutrition.

The study found that patients with mucormycosis had markedly lower levels of albumin compared with patients suffering from other fungal infections. Low albumin levels-known as hypoalbuminemia-were the strongest predictor of poor outcomes, including death, across patient populations spanning multiple continents.

“This is a remarkable finding and has the potential to change the way clinicians care for mucormycosis,” said Dr. Ibrahim, a senior author on the study. Essentially, the study identified hypoalbuminemia as a biomarker for identifying who would be at risk of developing this deadly disease. Therefore, patients can receive albumin loaded with free fatty acids to prevent the infection from taking place, which is the best way of dealing with mucormycosis given its aggressive nature.

“The study also tells us how albumin works on nullifying critical virulence factors including toxins and other fungal proteins involved in causing tissue damage and in aggressively invading human organs,” explained Dr. Ibrahim. The study raises the potential in pairing albumin therapy with immunotherapies that target Mucorales virulence factors for which The Lundquist Institute investigators are currently developing.

Researchers showed that albumin selectively inhibits Mucorales fungi, while leaving other microbes unaffected. Removing albumin from healthy human blood samples allowed the fungus to grow unrestricted, while mice lacking albumin were highly susceptible to infection. In contrast, restoring albumin levels protected against the disease.

Further experiments revealed that albumin exerts its antifungal effects through fatty acids bound to the protein, which disrupt fungal metabolism and protein production required for tissue invasion and disease progression. Blood samples from mucormycosis patients showed increased oxidation of these fatty acids, helping explain their vulnerability to infection.

The findings uncover a previously unknown host-defense mechanism and suggest that albumin-based therapies could offer a new strategy to prevent or treat mucormycosis, a disease with limited effective treatment options.

Reference:

Pikoulas, A., Morianos, I., Nidris, V. et al. Albumin orchestrates a natural host defence mechanism against mucormycosis. Nature 649, 693–702 (2026). https://doi.org/10.1038/s41586-025-09882-3.