Reach 2024: Do fungi pose a threat to our brains?
By Abeer Khan
A Q&A with Leah Cowen, program Co-Director of CIFAR’s Fungal Kingdom: Threats & Opportunities, on the realities of disease-causing pathogen spread on human health.
Fungi are fascinating organisms. They can grow fuzzy and in vivid colour, be used in the production of all kinds of foods and beverages, and even be critical components to many life-saving drugs. They can even degrade plastic. Fungi are also extraordinarily diverse, ranging from organisms so tiny they’re invisible to the naked eye, to those that encompass the Earth’s largest organism, Armillaria ostoyae, which is as massive as three blue whales.
Perhaps that’s why fungi are having a moment — both onscreen and in real life. A fungal pathogen known as Cordyceps, which can enter and control the mind of a specific species of ants, was at the centre of one of 2023’s most popular TV shows, The Last of Us. In the real world, fungal pathogens are becoming increasingly fatal, though none have exhibited zombie-inducing behaviours in humans — yet. A recent study found that nearly 4 million deaths per year are linked to fungal infections.
Why are these infections on the rise, and what threats do fungal pathogens pose to human and brain health? To find out, we spoke with Leah Cowen, Co-Director of our Fungal Kingdom: Threats & Opportunities program, whose work focuses on understanding what allows some microbes to exploit the host and cause disease.
Q: What made you interested in researching fungi?
LC: Fungi are cool! They are fascinating and understudied, providing a wonderful opportunity for fundamental discovery. The fungal kingdom is enormous, with incredibly diverse species and biology, and so many important mysteries to solve. Fungi have a huge impact on every aspect of life on the planet, from food security to biodiversity to human and brain health. What better set of organisms to work with?
Q: Are there any emerging trends that may impact how fungi may threaten human health?
LC: Yes. Our current estimates of fungal disease incidents and mortality rates are pretty imprecise as surveillance has been limited. What we do know is that fungi are becoming a bigger problem as fungal infections in humans increase. Fungi most often cause human disease when the host has a weakened immune system. That can happen due to different kinds of contexts, such as an infection with HIV — which can cause immunodeficiency — cancer treatment, or because of immunosuppressants used to tolerate transplants. With modern medical advances, we are keeping large patient populations alive much longer despite other underlying conditions, which is fantastic. But it means there's a growing population with immune deficiencies who are then vulnerable to infections.
Climate change is also poised to have a significant impact on infectious diseases. It has the potential to select new human pathogens and cause the spread of different ranges of current pathogens.
Photo: Josh Fee
Q: Many fungal infections occur outside the body, such as athlete's foot and ringworm. But what about inside the body?
LC: Although the higher temperature inside your body, compared to outside, limits the number of fungal species that can grow and cause disease, several fungal pathogens can evade your body’s defences and cause deadly diseases. One example is Invasive Aspergillosis, caused by a fungus called Aspergillus, which can cause a deadly lung disease. Another would be Candidiasis, which is caused by a fungus called Candida. Several species can cause bloodstream infections or systemic infections. And there's Cryptococcus, a species of fungus that causes cryptococcal meningitis, a very deadly brain infection.
Q: So, fungal infections can also occur in the brain?
LC: They certainly can. Fungal brain infections are typically called fungal meningitis. These can develop after a fungal infection moves or spreads from somewhere else in the body and into the brain or the spinal cord. Many species can cause these kinds of meningitis or brain infections, including Cryptococcus, Histoplasma, Blastomyces, Coccidioides and Candida species. Mucor species can also cause infections that spread to the brain.
Q: Why are fungal infections in the human body so difficult to treat?
LC: We have very few effective antifungal drugs. We have only three to four major classes to treat systemic fungal infections — which are in the body — compared to several dozen classes of antibacterials, where we still have a big need for new antimicrobials.
This is in part because fungi are closely related to humans and animals. This presents a challenge because it means that many potential drugs or molecules that inhibit something critical for the fungus to survive often target the same thing in the human host and are, therefore, extraordinarily toxic. It is also in part due to neglect of the fungal kingdom and very limited investment in antifungal drug discovery.
Q: Are there any emerging opportunities in research when it comes to fungi and the brain?
LC: There are all kinds of opportunities to better understand how fungi get into the brain, how they are cleared from the brain, and what kind of immune activity is happening. Some interesting findings have been made regarding when Candida gets into the brain, what mechanisms promote clearance, and whether there is any connectivity between fungal presence and inflammation, which could be relevant for neurodegenerative diseases.
We also know that fungi can modulate brain function. There are fungi called Cordyceps that infect the brain of a species of ants and modulate their behaviour, which is what inspired the show, The Last of Us. A better understanding of the relationship between fungi and brain infection will lead to more opportunities to think about interventions for these deadly infections.
Q: What research on fungal disease do you think needs to happen in the next five to ten years?
LC: We've only just begun to improve our surveillance of fungal disease. More work can be done on reporting and surveillance of fungi that are causing disease. We also need to worry about more than just humans, because many fungi can move between different kinds of organisms. We also need to think carefully about how we globally transport plants and animals because they are also often vectors for disease.
As a result, it is critical to enhance funding for research on fungal pathogens. To do this, we need to develop programs to support partnerships between industry and academia. No single academic lab can advance the full continuum of research and development of therapeutics needed to address human disease and brain health — it requires partnerships with industry.
Q: What excites you about your work and what are you most looking forward to achieving moving forward?
LC: I am deeply passionate about leading amazing teams. Working closely in partnership with the next generation is one of the most exciting parts of this job. We are committed to thinking big, asking big questions and taking innovative and interdisciplinary approaches to solving grand challenges that are presented by the fungal kingdom.
I am also very excited about continuing to lead our CIFAR program, which is a wonderful opportunity for transformative impact. The CIFAR model of bringing together the best minds from around the world to convene global, interdisciplinary teams to tackle the grand challenges of our time allows us to advance the field in amazing ways.
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