Researchers take aim at hard-to-treat fungal infections

Nov 19, 2009
Reeta Prusty Rao is an assistant professor of biology and biotechnology at Worcester Polytechnic Institute. Credit: Patrick O'Connor

A team of researchers at the Worcester Polytechnic Institute Life Sciences and Bioengineering Center at Gateway Park has developed a new model system to study fungal infections. The system can be a powerful tool for screening potential drug targets for conditions like thrush, athlete's foot and vaginal yeast infections, which affect millions of people each year but are difficult to treat with existing medications. Using the new model, the researchers also identified a gene that may be a promising target for a new anti-fungal drug.

The WPI research team led by Reeta Prusty Rao, PhD, assistant professor of biology and biotechnology, developed the new model using the microscopic soil worm Ceanorhaditis elegans (C. elegans) as a test host which is then infected with the Saccharomyces cerevisiae (S. cerevisiae). Commonly known as baker's or brewer's yeast, S. cerevisae doesn't cause disease in humans, but the WPI team found that it can infect, and if left untreated, kill the worm. Since S.cerveisiae has many genes in common with fungi that do cause human disease, the genetic and molecular analysis now possible with this new testing model can be used to identify targets that could prevent or treat fungal infections in people.

"The beauty of this new model is that we can study both sides of the equation: the processes of and the host's response to try and fight off that infection," said Prusty Rao.

Fungal infections are persistent and are not easily cleared by the handful of drugs currently available to treat them. As a result, the infections often reoccur. Typically, common fungal infections like athlete's foot and vaginal yeast infections do not cause serious harm. However, when an infection spreads to the , it can be deadly. Hospitalized patients with catheters or central intravenous lines are at risk, as the fungi can grow on those devices and enter the body. Because of the lack of an effective treatment, the mortality rate for some systemic fungal infections is nearly 45 percent.

In their recently published study, Prusty Rao's team, working in collaboration with Samuel Politz, PhD, associate professor of biology and biotechnology at WPI, used a range of available genetic tools to monitor the infection process and observe how the worm tried to defend itself against the infection. They also studied which genes in the yeast were involved in trying to fight back against the worm's defense mechanisms. The team reported their findings in the paper "A Pathogenesis Assay Using Saccharomyces cerevisiae and Caenorhabditis elegans Reveals Novel Roles for Yeast AP-1, Yap1, and Host Dual Oxidase BLI-3 in Fungal Pathogenesis" published by the journal Eukaryotic Cell.

The work showed that the worms produce hydrogen peroxide and other so-called reactive oxygen species (ROS) to try and kill the invading fungus, while certain in the yeast produce other chemicals that can ward off the hydrogen peroxide attack. One gene in particular, called Yap 1, was found to be essential for the yeast's ability to neutralize the ROS attack. When they removed Yap 1 from the yeast's genome, infection was prevented. This was an important finding because Yap 1 is found only in fungi, not people. If a drug can be developed to target only that gene, it should not have any side-effects in people.

"The challenge has been to find therapeutic agents that can kill the fungus, but not harm the surrounding tissue; that's proven to be very difficult," Prusty Rao said. "In this study, we show that the gene Yap 1 is essential for infection, and it is only found in yeast, including the strains that do cause disease in people. So this is a promising target for further study."

Source: Worcester Polytechnic Institute (news : web)

Explore further: Research sheds light on what causes cells to divide

add to favorites email to friend print save as pdf

Related Stories

Mounting a multi-layered attack on fungal infections

Sep 08, 2009

Unravelling a microbe's multilayer defence mechanisms could lead to effective new treatments for potentially lethal fungal infections in cancer patients and others whose natural immunity is weakened.

New Way to Fight Fungal Infection

Jun 23, 2009

( -- A team of researchers led by Amy G. Hise, M.D., M.P.H., assistant professor at the Center for Global Health and Diseases at Case Western Reserve University's School of Medicine, has discovered how the body ...

Gamma interferon could aid fight against fungal infections

Oct 31, 2007

Interferon, the “superhero” cure for viral infections, may be a strong weapon in the battle against fungal infections in immunocompromised patients, according to an article in the November issue of Microbiology Today.

Recommended for you

Research sheds light on what causes cells to divide

14 hours ago

When a rapidly-growing cell divides into two smaller cells, what triggers the split? Is it the size the growing cell eventually reaches? Or is the real trigger the time period over which the cell keeps growing ...

Locking mechanism found for 'scissors' that cut DNA

14 hours ago

Researchers at Johns Hopkins have discovered what keeps an enzyme from becoming overzealous in its clipping of DNA. Since controlled clipping is required for the production of specialized immune system proteins, ...

Scrapie could breach the species barrier

18 hours ago

INRA scientists have shown for the first time that the pathogens responsible for scrapie in small ruminants (prions) have the potential to convert the human prion protein from a healthy state to a pathological ...

Extracting bioactive compounds from marine microalgae

19 hours ago

Microalgae can produce high value health compounds like omega-3s , traditionally sourced from fish. With declining fish stocks, an alternative source is imperative. Published in the Pertanika Journal of Tr ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.