Can a Deadly Fungus Become Our Protector? How Scientists are Repurposing Candida
"Turning a Pathogen into a Shield: Exploring the potential of Candida albicans to boost immunity and fight infections"
Candida albicans, a common yeast found in the human body, usually lives peacefully as part of our microbiota. While it typically doesn't cause problems, it's also a major fungal pathogen, responsible for both superficial and life-threatening disseminated infections. Scientists have primarily focused on understanding its harmful aspects, but a new perspective is emerging: could C. albicans be harnessed for beneficial purposes?
One challenge in studying the potential benefits of C. albicans is that it doesn't naturally colonize most laboratory animals, like mice, unless their gut microbiota is disrupted by antibiotics. However, when C. albicans enters the bloodstream of mice, it becomes highly virulent. This duality has made it difficult to study the commensal (harmless) state of the fungus and any potential mutualistic interactions with a healthy host.
Now, researchers have ingeniously used this dichotomy to their advantage. By serially passaging C. albicans in the GI tracts of antibiotic-treated mice, they've successfully evolved the fungus into a genuine commensal organism. This modified C. albicans not only coexists peacefully within the host but also provides protection against other dangerous pathogens, potentially opening doors to universal vaccines.
From Foe to Friend: Evolving Candida for Commensalism and Protection
The key to this transformation lies in the yeast-to-hypha transition, a crucial aspect of C. albicans virulence. This fungus can switch between a yeast form, which aids in bloodstream dissemination and tissue adhesion, and a filamentous hyphal form, which promotes tissue invasion and escape from immune cells. The researchers found that the evolved C. albicans variants exhibited defects in this transition, favoring the yeast form.
- Enhanced Gut Colonization: Evolved C. albicans variants thrive in the GI tract, even without antibiotic-induced dysbiosis.
- Reduced Virulence: These variants show decreased ability to cause blood-borne infections.
- Cross-Protection: Colonization or injection of these variants protects mice against virulent C. albicans, as well as other pathogens like Aspergillus fumigatus, Pseudomonas aeruginosa, and Staphylococcus aureus.
Trained Immunity: A New Avenue for Disease Prevention?
The evolved C. albicans variants not only protect against fungal infections but also offer cross-protection against bacterial pathogens. This protection is rapid, independent of adaptive immunity, relatively short-lived, and requires cytokine production – all hallmarks of 'trained immunity.' This recently discovered property allows enhanced innate immune cell responses upon re-encountering pathogens.
While C. albicans colonization was already known to protect against subsequent injury and infection, these new variants offer increased cross-protection compared to both the parental strain and yeast-to-hypha switch mutants. This suggests that passage through the gut leads to changes beyond filamentation that contribute to triggering trained immunity. These changes may involve modifications to the fungal cell wall, particularly β-glucans, which are strong inducers of trained immunity.
Understanding the precise nature of these changes is crucial for developing a universal vaccine based on the cross-protection properties of these C. albicans variants. Although a universal vaccine might seem ambitious, further exploration of the mechanisms by which these variants protect against different fungal infections could lead to innovative preventive approaches. Such approaches are urgently needed, as fungal infections cause up to a million deaths per year globally, and antifungal resistance is on the rise.