Deadly Fungus Can Shape-shift Its Way Deep into Your Brain: 'Shocked'

A fungus that can change its shape to fit into your brain has been discovered by scientists.

Cryptococcus neoformans (C. neoformans), a pathogenic fungus, can shape-shift itself to fit through the blood-brain barrier, a layer of protection used to keep pathogens out of the brain, according to a paper published in the journal Cell Host & Microbe.

"The changes that it undergoes when it first enters the body are pretty incredible and we're still trying to understand it," Jessica Brown, a pathologist from the University of Utah and co-author of the paper, told Newsweek.

C. neoformans can be found in nature living on rotting wood or in bird droppings. According to the CDC, if the fungus is inhaled it can infect the lungs and other organs, including the brain, leading to cryptococcal meningitis.

The researchers found that the smallest cells of C. neoformans ended up in the brains of mice they were studying, and that the surfaces of these small cells changed when they entered the brain.

"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," Brown said in a statement.

"We demonstrate that the formation of a small C. neoformans morphotype—called 'seed' cells due to their colonizing ability—is critical for extrapulmonary organ entry," wrote the authors in the paper. "Seed cells exhibit changes in fungal cell size and surface expression that result in an enhanced macrophage update."

These seed cells have an altered cell surface that causes them to be taken up by macrophages (immune cells), according to Brown.

"In a number of tissues, macrophages are responsible for containing invaders, so they will take them up and attempt to sequester and destroy the invader," she said.

"We think that seed cells exploit this tendency, are carried by the macrophage into the organ more readily, and then escape and grow in their new organ environment if the conditions are favorable, as they are in the brain."

According to Brown, after a seed cell enters the brain, the first type of cells to form are called titan cells because they are gigantic, containing at least four times as many copies of DNA as a "normal" C. neoformans cell.

"These titan cells form directly from the infecting [seed] cells," Brown told Newsweek. "The seed cells that we study, the small ones that enter the brain, probably don't form when another cell shrinks.

"Instead, we think that seed cells form across generations: a normal or titan cell receives a signal, then when it next divides to form a new cell, it makes a seed cell as its progeny instead of a cell just like itself. The seed cells likely then form more seed cells when they divide."

The fungus has been previously found to increase its cell mass by up to 10 times inside the human lung, so the fact that it can enter the brain is concerning.

"The scary thing about this fungus is that we don't think that it wants to get inside the brain per se," Brown said. "It's not passed from person to person, so there isn't really any evolutionary selection for growing inside a person as there are with, for example, respiratory viruses.

"Instead, we think that this is an evolutionary accident. C. neoformans grows extremely well on inositol, which is found in large quantities in the spinal fluid, spinal cord, and brain tissue. This might be a result of C. neoformans' natural environment, which is soil, trees, and bird droppings, as plant matter is high in inositol."

"We therefore think that C. neoformans acquired the ability to grow on inositol in its environmental niche and that ability ends up being problematic when people are infected, since when C. neoformans reaches the inositol-rich central nervous system, it grows well and there isn't much to stop it from doing so."

The researchers are concerned that the effects of climate change may make C. neoformans more proficient at infecting humans.

"A concern in the future is that as the climate changes, microbes such as fungi will become more adapted to stressful conditions (temperature extremes, drought, etc.) that will increase their ability to survive the stressful conditions within the human body," Brown said.

However, the researchers also hope that their discovery could lead to new strategies for blocking C. neoformans infection.