Targeting Genes Could Remove the Fungus Among Us
Posted by Lauren Rugani on December 30, 2009
New research that investigates how fungi infect host organisms on genetic and molecular levels could one day lead to anti-fungal drugs that are far more efficient than current treatments. Scientists at Worcester Polytechnic Institute in Massachusetts have begun to understand not only how fungi infect an organism but how the host fights back – and whether or not it works.
Millions of people suffer each year from fungal infections, ranging from common skin rashes like athlete’s foot and ringworm to dangerous systemic infections like cryptococcal menengitis, which affects about 5 in every million people per year in the United States. While contracted relatively easily through skin contact or inhalation, fungal infections are difficult to cure – an estimated 10000 deaths per year result from infections that, when left untreated, spread throughout the body.
Symptoms can be treated with topical or systemic remedies that, like any drug, exploit the differences between fungal and human cells to destroy the disease. But unlike bacteria, fungi and humans are both eukaryotes and are extremely similar at the molecular level, so drugs that kill fungal cells also have an adverse affect on human cells. Treatments, therefore, often have dangerous side effects including liver damage, altered hormone levels, severe allergic reactions or anaphylaxis.
The WPI group found a genetic component exclusive to fungi that could provide the basis for new, safer drug therapies. They infected a tiny worm called C. elegans with baker’s yeast, a common fungus benign to humans but able to infect and kill the worm if left untreated. With a variety of genetic tools, the team monitored how the fungus infected the worm, how the worm tried to defend itself and, in turn, how the fungus fought off these defenses. They found that the worms produced reactive oxygen species like hydrogen peroxide, but genes in the yeast counterattacked with other chemicals. A particular gene called YAP 1 – the one that is found in fungi but not in humans – was key for the yeast’s response to the worm’s attack. When this gene was removed, the worm’s defense worked and prevented infection.
While yeast doesn’t harm humans, it shares many genes (including YAP 1) with fungi that do cause disease. Developing a drug that targets this specific gene could help cure fungal infections without the harmful side effects of today’s medicines.