Glucose-regulated Protein may Be Responsible for Mucormyosis Infection in Diabetics

Researchers at the University of California, Los Angeles, led by Ashraf Ibrahim, have discovered data in mice that may explain why patients with diabetes, particularly patients who also have diabetic ketoacidosis (DKA), are so susceptible to mucormyosis, a life-threatening infection that affects the sinuses, brain, and lungs.

The researchers aimed to determine “the endothelial cell receptor(s) for fungi of the order Mucorales (the fungi that cause mucormyosis,” according to the Journal of Clinical Investigation article on the study. The team discovered that the glucose-regulated protein 78 (GRP78) may be “a novel host receptor that mediates invasion and damage of human endothelial cells by Rhizopus oryzae, the most common etiologic species of Mucorales.”

As the researchers observed “human blood vessel-lining cells cultured in levels of glucose and iron consistent with those seen during DKA and in the tissues that are affected during mucormycosis in mice with DKA” — both environments that are susceptible to mucormyosis — they saw increased levels of expression of GRP78. When the researchers treated the mice with DKA with a GRP78-specific immune serum, they were protected from mucormyosis.

The researchers cite the efficacy of the immune serum as the “most important” element of the conclusions reached. The next step in discovering the role that the GRP78 protein plays in mucormyosis infection is to determine the mechanism of immunological protection, which the researchers are currently working on.

“These results provide insight into why patients with DKA are uniquely susceptible to mucormycosis infections and provide a foundation for therapeutic interventions against extremely lethal mucormycosis,” the researchers conclude in the Journal of Clinical Investigation article.

Mucormyosis infection causes a mortality rate of at least 50%, according to the researchers.

Ibrahim works in the David Geffen School of Medicine at UCLA and the Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center.