Snails are slow-moving creatures that can’t flee inhospitable environments. Instead, they rely on biomolecular defences against pathogens – biomolecules that could one day be harnessed to fight a fungus that kills tens of thousands of people a year.
Although there are various antifungal medications on the market, Cryptococcus neoformans can develop resistance to them, especially during long courses of treatment. People with compromised immune systems, such as those with HIV/AIDS or cancer, are particularly at risk.
It doesn’t help matters that C. neoformans can be found just about everywhere. It lives in soils, decaying wood and even in eucalyptus trees and pigeon droppings.
But research led by Davier Gutierrez-Gongora, a University of Guelph molecular biology PhD student, and his supervisor, Dr. Jennifer Geddes-McAlister, recently found compounds extracted from three snail species in southwestern Ontario interfered with mechanisms C. neoformans relies on to invade and survive in human tissues.
What’s more, the compounds in snail extracts work in a way that makes it less likely the fungus will develop resistance. Instead of attacking the fungus itself, the compounds block some of the mechanisms the fungus uses to spread and defend itself from the host.
These mechanisms include making melanin, which helps it grow beyond its optimal temperature of 30°C. This is important because the human body runs at about 37°C.
The fungus can also produce biofilms which it coats itself with as protection from our body’s immune system, and it can produce enzymes to break down human tissue so it can feed off its host’s nutrients.
“If the fungus secretes an enzyme for example to degrade the host tissue, and we stop those enzymes from working, it doesn’t impede the fungi but it empowers the host to clear the pathogen,” says Geddes-McAlister. “That’s the perspective we take – empowering the host.”
Attacking these mechanisms, called virulence factors, is a growing area of research in response to drug-resistant diseases, but most scientists focus on fighting bacteria. That’s because bacterial infections are more prevalent, affecting both healthy and immune compromised people and are implicated in more than three times as many deaths. Geddes-McAlister’s team is one of the few that focuses on anti-virulence of fungi.
One of the biggest hurdles to designing anti-fungal medications is the close relationship between fungus and humans. “We are both eukaryotes, and we share similar cell organization and pathways,” says Geddes-McAlister.
That means anything toxic to the fungus might also be toxic to us. But since snails are also eukaryotes and their compounds are not toxic to them, they shouldn’t be a problem for us either. In fact, the team tested the snail compounds on mouse immune cells and found no serious effects.
However, the study, published in the journal Scientific Reports, did yield one surprise. Geddes-McAlister had expected each species of snail to have evolved compounds that used very similar pathways for disarming the fungus. Instead, each species – the introduced grove snail, the invasive Chinese mystery snail and the native ramshorn snail – attacked different fungal mechanisms.
This means there’s potential for using a cocktail of snail-derived compounds in treating human fungal infections, which could lead to particularly powerful drugs.
The next step, says Geddes-McAlister, is to identify the active ingredients in each compound before testing them in isolation and in combination.
Dr. Matthew Kimber, a molecular biologist with the University of Guelph who was not involved in Geddes-McAlister’s research agrees there is so much more to learn from the defences that diverse organisms, including snails, have evolved to fight off pathogenic fungi.
“Not only is there the potential for discovering therapeutically useful antifungal compounds, but studying the exact mechanisms by which these biomolecules interfere with their targets may reveal potentially druggable weaknesses in the biology of pathogenic fungi that we had not previously considered,” he says.