An international team of scientists has discovered that albumin, the most abundant protein circulating in human blood, plays a powerful and previously unrecognized role in protecting the body from mucormycosis, a rare but frequently deadly fungal infection. The findings were published in Nature. The research was led by George Chamilos, MD, and his team at the University of Crete and the Institute of Molecular Biology and Biotechnology, with key contributions from a group at The Lundquist Institute for Biomedical Innovation led by Professor Ashraf Ibrahim, PhD.
Mucormycosis, often referred to as “black fungus,” is caused by Mucorales fungi and can spread rapidly through the body. The infection is fatal in up to half of cases, and in some patients, a diagnosis carries an almost certain risk of death. Cases surged in India during the COVID-19 pandemic, particularly among people with diabetes, compromised immune systems, or malnutrition.
Low Albumin Levels Linked to Higher Death Risk
The researchers found that patients diagnosed with mucormycosis had significantly lower albumin levels compared with patients battling other fungal infections. Low albumin levels — known as hypoalbuminemia — emerged as the strongest predictor of severe outcomes, including death, across diverse patient groups on 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 of the study. The results point to hypoalbuminemia as a biomarker that could help doctors identify people at high risk of developing this aggressive infection. According to the findings, providing patients with albumin enriched with free fatty acids may help prevent the infection from taking hold, an important strategy given how quickly mucormycosis progresses.
How Albumin Blocks Fungal Invasion
“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 research also opens the possibility of combining albumin treatment with immunotherapies designed to target Mucorales virulence factors, which investigators at The Lundquist Institute are currently developing.
Laboratory experiments showed that albumin specifically suppresses the growth of Mucorales fungi without interfering with other microbes. When albumin was removed from healthy human blood samples, the fungus multiplied freely. Mice that lacked albumin were highly vulnerable to infection, while restoring albumin levels offered significant protection.
Fatty Acids Play a Key Role
Additional testing revealed that albumin’s antifungal activity depends on fatty acids attached to the protein. These fatty acids interfere with fungal metabolism and block the production of proteins needed for tissue invasion and disease progression. Blood samples from patients with mucormycosis showed higher levels of fatty acid oxidation, which may help explain why they were more susceptible to infection.
Together, the findings reveal a previously unknown natural defense mechanism within the human body. They also suggest that albumin-based therapies could provide a much-needed new approach to preventing or treating mucormycosis, a disease that currently has limited effective treatment options.