Meningitis is a brain disease, which causes around 1 million people each year. It is caused by the fungus Cryptococcus and most of the deaths occur when immune system is impaired because of AIDS, cancer treatment or an organ transplant.
It is extremely difficult to treat this disease, because fungi are genetically similar to humans, which means that compounds that fight these fungi have toxic side effects for patients too. However, now scientists the University of Wisconsin-Madison might have found a way to prevent diseases caused by fungi.
Researchers performed a very detailed study to better the understanding about how a dormant fungal spore transforms itself into disease-causing yeast. They found 18 proteins that play a role in spore formation and germination. This discovery may help to develop novel treatments for diseases caused by fungi or prevent them by blocking the spores’ germination.
These diseases are caused by spores – tough, resilient capsules that are made via sexual reproduction on trees or soil. They can remain dormant for years and usually, like in case of Cryptococcus, are harmless until they get carried away by the wind or water and get somewhere, where they can transform themselves into a yeast cells.
Christina Hull, lead author of the study, explained that “when you inhale a spore, if it can’t grow, it can’t cause disease Spores are dormant; they hang out until they find a place to grow into yeast, and the human lung is a good place. From there, the yeast can travel to the brain.” At the time when first symptoms if meningitis appear, patient already has billions of Cryptococcus yeasts growing in the brain. Scientists think that by preventing spores from activating, they could help immunocompromised patients to avoid the disease.
Up until now it was rather difficult to research issue of germination of Cryptococcus spores, because they are extremely difficult to isolate them from other cell types. The transformation from spore to yeast is a huge change; therefore many things have to happen for this process to occur. Spores are very tough – they have a thick, protective coat. It must be broken down for the spore to change into a completely different cell type.
If this process could be prevented, spore would not transform into yeast and diseases could be avoided. But in order to do that, scientists have to know which molecules allow spore to break down its protective coat. In order to figure this out, researchers deleted the genes for the 18 proteins in question and studied the resulting mutants. Scientists were surprised to understand that that most of the genes are involved in the process that forms a spore in the first place.
While growing these mutant spores, scientists paid more attention to one gene that is necessary specifically for germination. Now scientists are looking for potential drug candidate or even already existing drug on the market that could prevent spores from germinating. They say that these new finding may help them to fight other diseases cause by fungi as well. For example, some forms of childhood asthma are caused by by mold (a common term for some fungi). Betering the understanding about how spores germinate could help treating or maybe even preventing some types of childhood asthma.
Such research was impossible just a few years ago. But advancements in in high-precision mass spectrometry and invention of microscale fluid flow devices allowed scientists to develop and test antifungal compounds that inhibit spore germination. Eventually it should lead to effective preventive measures. If spore enters the lungs, but cannot grow and germinate, it cannot cause a disease. This is why this discovery may eventually prevent such diseases as meningitis, some forms of childhood asthma and others.