Albumin Identified as Defense Against Deadly "Black Fungus"
An international study published in Nature has identified albumin, a protein abundant in human blood, as a defense against mucormycosis, a severe fungal infection. The groundbreaking research was led by George Chamilos, MD, at the University of Crete and Institute of Molecular Biology and Biotechnology, with significant contributions from a Lundquist Institute for Biomedical Innovation team led by Professor Ashraf Ibrahim, PhD.
Understanding Mucormycosis
Mucormycosis, also known as "black fungus," is a rapidly progressing infection caused by Mucorales fungi. It carries a high fatality rate, sometimes exceeding 50% of affected patients. The disease saw a significant increase in India during the COVID-19 pandemic, particularly impacting individuals with diabetes, weakened immune systems, or malnutrition.
"Patients with mucormycosis exhibited significantly lower albumin levels compared to those with other fungal infections. Low albumin levels, termed hypoalbuminemia, were identified as the strongest predictor of adverse outcomes, including mortality across diverse patient populations globally."
Albumin Levels as a Key Predictor
The study found that patients with mucormycosis exhibited significantly lower albumin levels compared to those with other fungal infections. Low albumin levels, termed hypoalbuminemia, were identified as the strongest predictor of adverse outcomes, including mortality, across diverse patient populations globally.
Researchers suggest that hypoalbuminemia could serve as a biomarker to identify individuals at risk of developing mucormycosis. This finding indicates that administering albumin loaded with free fatty acids could potentially prevent the infection.
Mechanism of Action: How Albumin Fights Back
Dr. Ibrahim explained that albumin neutralizes critical virulence factors of the fungi, such as toxins and other proteins that contribute to tissue damage and aggressive invasion of human organs. The study also explores the potential of combining albumin therapy with immunotherapies targeting Mucorales virulence factors.
"Albumin neutralizes critical virulence factors of the fungi, such as toxins and other proteins that contribute to tissue damage and aggressive invasion of human organs."
Experimental Validation
Experiments demonstrated that albumin specifically inhibits Mucorales fungi without affecting other microbes. Removing albumin from healthy human blood samples allowed the fungus to grow unchecked, while mice lacking albumin were highly susceptible to infection. Conversely, restoring albumin levels provided protection against the disease.
Further analysis revealed that albumin's antifungal effects are mediated by fatty acids bound to the protein. These fatty acids disrupt fungal metabolism and protein production essential for tissue invasion and disease progression. Blood samples from mucormycosis patients showed increased oxidation of these fatty acids, which may explain their vulnerability to the infection.
Future Therapeutic Potential
These findings suggest a previously unknown host-defense mechanism and propose that albumin-based therapies could offer a new strategy for the prevention or treatment of mucormycosis, a disease with limited current treatment options.
"These findings suggest a previously unknown host-defense mechanism and propose that albumin-based therapies could offer a new strategy for the prevention or treatment of mucormycosis, a disease with limited current treatment options."