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Finding the Line of Yeast Resistance

Scientists identify gene that enables fungi to grow on plastic medical implants

SUNDAY, May 13 (HealthScout) -- Scientists have found a gene that enables infectious fungi to stick to plastic medical devices and cause serious complications in patients with such plastic implants as hip replacements and heart valves.

Thousands of patients die each year because of these fungal infections, also known as "biofilm formations."

Often the only way to treat the problem is to remove the implant. But researchers at the Whitehead Institute for Biomedical Research in Cambridge, Mass., hope that by identifying the gene that allows the fungi to grow, new treatments can be found to prevent the formations.

"When [fungi are] growing in this biofilm form, they're more resistant to antibiotics than when they're free-floating or just when they're invading into the tissue," says lead researcher Todd Reynolds, a postdoctoral fellow at Whitehead, which is affiliated with the Massachusetts Institute of Technology.

"And the danger there is you can clear the infection from the rest of the body but you can't get rid of it in this plastic implant because [the infections are] more resistant when they're growing in that form."

"As a result, it sets up a chronic infection, so that it will flare up from time to time unless you actually remove the implant and get rid of the infection," Reynolds adds.

Reynolds worked with the baker's yeast Saccharomyces cerevisiae, which behaves like such dangerous fungal infections as Candida.

Reynolds first grew the yeast in a gel-like substance and the yeast spread into beautiful floral patterns. Reynolds pinpointed the gene FLO11 as the gene that creates those floral patterns and also allows the yeast to stick to hard plastic surfaces.

"What we found is that in specific conditions, this yeast can adhere or attach itself to plastic and begin growing on plastic. It doesn't feed off the plastic but it stays attached to it while it's feeding off the nutrients in the liquid that surrounds it," Reynolds says.

When he neutralized the FLO11 gene, the yeast no longer formed the wide-spreading floral patterns and wasn't able to stick to hard plastic surfaces.

The study was published in a recent issue of the journal Science.

Reynolds says the FLO11 gene belongs to a large family of genes present in many pathogenic fungi.

While they've pinpointed the FLO11 gene, Reynolds says the researchers don't understand exactly how the fungi attach to plastic.

The researchers are now using DNA chips -- which resemble microscope slides and allow scientists to analyze the activities of thousands of genes simultaneously -- in an effort to understand how FLO11 works in conjunction with other genes to enable fungi to stick to plastic.

"What we're really interested in doing is to understand the biology and the mechanism by which this gene operates and other genes, which may contribute to it, or help it function or even compensate for it in certain circumstances," Reynolds says.

"The more we know about it, the more options we have for drug treatments," he adds.

Peter Hecht, CEO of Microbia, a Cambridge-based company that develops drug therapies to treat different kinds of fungal infections, says, "We think [Reynolds'] technology is quite good and we've licensed commercialization rights to it."

Current therapies for biofilm infections are expensive, highly toxic and not very effective, Hecht adds.

One potential approach would be to develop drugs that neutralize the FLO11 gene. But Hecht notes researchers have also uncovered a large network of cellular components that regulate the activity of FLO11.

"So that actually gives us a very large number, probably close to 50 drug targets," Hecht says.

What To Do

For more information about biofilms, go to this listing of biofilm sites, or the American Society for Microbiology.

For more HealthScout stories on fungi, click here.

SOURCES: Interviews with Todd Reynolds, Ph.D., postdoctoral fellow, Whitehead Institute for Biomedical Research; Peter Hecht, Ph.D., CEO, Microbia; both in Cambridge, Mass.; Feb. 2 issue of Science journal.
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