This fungus shrinks in size to better infect the brain: Finding could spur new strategies to prevent the leading cause of fungal meningitis

A fungus that is a common cause of fungal meningitis undergoes a remarkable transformation once it enters the body, allowing it to infect the brain, according to new research by scientists at University of Utah Health. Studies in mice show that as the fungal intruder travels through the body, it shrinks and acquires characteristics that help infection to spread, all in a matter of days.

The discovery could lead to new strategies for blocking Cryptococcus neoformans infection and preventing detrimental effects on the host. C. neoformans is the leading cause of a rare but deadly swelling of the brain that occurs in people with weakened immune systems.

“Cryptococcus cells in the lungs are very diverse with different sizes and different appearances. So, when my graduate student showed me pictures of the uniformity of cells from the brain, I was shocked,” says Jessica Brown, Ph.D., associate professor of pathology at U of U Health and the study’s senior author. “It suggested that there was some very strong reason why only this population of cells were making it that far into the body.” Her former graduate student, Steven Denham, PhD, is leading author on the study. Their research recently published online in the peer-reviewed journal Cell Host & Microbe.

The fungus adapts rapidly to withstand microenvironments in the body

Brown’s fascination with the funguscame from the observation that it thrives in so many different habitats. In the wild, the organism lives in rotting wood and bird droppings. If it is inadvertently inhaled, the fungus can survive in the lungs and then travel in the bloodstream to the brain and other organs, each of which has its own challenging micro-environment.

Previously, other scientists found that the fungus copes with living in the lungs by growing to 10 times its normal size, presumably becoming too large for the host immune system to destroy. But in other parts of the body, fungal cells are much smaller. Brown wondered, could the cells’ extra-small size be another type of advantage? Perhaps that characteristic helps them colonize other organs, such as the brain.

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