Researchers at Albert Einstein College of Medicine of Yeshiva University have discovered how a fatal fungus evades the human immune system and causes disease.
Cryptococcus neoformans typically gains access through the lungs and can then spread throughout the body including the brain. Scientists have known that the capsule surrounding the fungus is essential to its ability to cause disease.
“But we didn’t understand the mechanism responsible for capsule growth,” says senior author, Arturo Casadevall, M.D., Ph.D. “As the capsule grows larger, it reaches a point where immune system scavenger cells, known as macrophages, can’t swallow it.”
Investigators used dynamic light scattering and determined that the capsule, composed of polysaccharides, grows by linking saccharides together at its outer edge, forming giant molecules pointing in an outward direction.
Polysaccharides are poorly understood, partly because they are difficult to work with. “Also, scientists have tended to view polysaccharides as boring molecules that simply grow to a specified length,” adds Dr. Casadevall.
“But this study raises huge questions about polysaccharides,” he continues. “For example, how does the organism assemble these molecules, and how does it know how to make molecules that are roughly the same length? We don’t know. There appears to be a whole dimension of cellular machinery that we never knew existed.”
The research appears in the January 27 issue of the Proceedings of the National Academy of Sciences.