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Study Yields Insights Into Pathogenic Fungi -- And Beer

Date:
August 12, 2005
Source:
Whitehead Institute for Biomedical Research
Summary:
Chemotherapy and organ transplantation not only take a huge toll on patients, but they can compromise the immune system and leave patients vulnerable to infections from microbes such as pathogenic fungi -- the fastest-growing cause of hospital-acquired infections. Now researchers from Whitehead Institute for Biomedical Research have discovered one possible reason why these fungal microbes are such a scourge.
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Chemotherapy and organ transplantation not only take a huge toll onpatients, but they can compromise the immune system and leave patientsvulnerable to infections from microbes such as pathogenic fungi--thefastest-growing cause of hospital-acquired infections. Now researchersfrom Whitehead Institute for Biomedical Research have discovered onepossible reason why these fungal microbes are such a scourge.

According to the research appearing in the August 7 online editionof the journal Nature Genetics, fungal microbes can quickly alter theappearance of their cell surfaces, their "skin," disguising themselvesin order to slip past the immune system's vigilant defenses. And, forall the world's brewers, the study also helps explain why certain beersare cloudy and others are clear.

"It's all about skin," says Whitehead Member Gerald Fink, whocompares the fungal microbe to an M&M--a sugar coating encasing thecell's DNA. "The skin of fungi microbes is what enables them to stickto your organs, and thus become pathogenic. It also enables the fungito stick together, which is desirable for fermentation in beer."

The genetic core to this study is a DNA phenomenon known astandem repeats. Here, small units of between 3 and 200 nucleotides formwithin a gene and repeat sometimes up to about 35 times. (Nucleotides,the building blocks of our genome, are represented by the letters A, C,T, G.) In humans, these tandem repeats received a lot of attention whenthe gene responsible for Huntington's disease was discovered; a repeatof the letters CAG in a gene called IT-15 causes the condition.

These tandem repeats also occur in fungal microbes. KevinVerstrepen, a post-doctoral researcher in Fink's lab, decided to findout how often they occur, and what possible functions they might offer,by using baker's yeast as a model. Verstrepen scanned the entire yeastgenome with a custom computer program developed by Whitehead'sbioinformatics group. He discovered that these repeats are commonthroughout the yeast genome, and that more than 60 percent occur ingenes that code for cell-surface, or skin, proteins. In other words,"most of these repeats somehow affect how the yeast cell interacts withthe environment surrounding it," says Verstrepen.

In addition, he found that the length of these repeats variedgreatly between a mother and a daughter cell. While one yeast cellmight have a 20-unit repeat on a particular gene, when it divides, thenew cell might have only a five-unit repeat on that same gene. Andsubsequently, when that cell then divides, its daughter cell might goback to 20 repeats. "It's like an accordion," says Verstrepen. "Ourstudy really showed how quickly and easily these repeats can recombine,altering the properties of the cell surface almost immediately."

This provides a significant clue into why fungal infectionscan often be so deadly. The immune system generally recognizes invadersby certain signatures on their outer coatings, such as proteinconformations. However, if these fungal microbes can quickly change theshape of these proteins by changing the number of repeats in thecorresponding gene, they can then manage to stay one step ahead of ourbody's defenses.

"It's important to remember," says Fink, "that these microbeshave been around for billions of years. They haven't come this farwithout learning how to fight off predators."

Verstrepen and his colleagues took this research a stepfurther, focusing on a gene called FLO1, a cell-surface gene common toboth baker's yeast and pathogenic fungi. FLO1 creates the conditionsthat enable yeast cells to adhere to surfaces. It's also the gene thatallows pathogenic fungi to stick to host tissue. The researchersdiscovered a clear correlation between the number of repeats in FLO1and the degree to which these cells could adhere to a surface. WhenFLO1 contained many repeats, it adhered vigorously to a plasticsurface. As the number of repeats declined, so did its ability toadhere.

Fink believes that these findings show why traditionalapproaches to targeting drugs won't work on fungal microbes. Thefeatures that drugs target may be exactly the ones that change soreadily. "We need to target other aspects to the cell surface thatdon't change," says Fink, suggesting that certain sugar moleculesresiding on the inside of the cell coating may be valuable targets.

The research also may help to reveal why certain strains of yeast brew better beers.

Both Verstrepen and Fink have consulted for a number ofcommercial brewers. "Brewers have been cultivating certain strains ofyeast for hundreds of years," says Fink. "The secret of a good, fresh,clear beer--the kind that Americans tend to like--is that the yeastcells all stick together." When yeast cells don't adhere, the beertends to cloud up. "We now know that these tandem repeats are themolecular mechanism that yields good beer."

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This research was supported by a grant from the U.S. National Institutes of Health.


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Materials provided by Whitehead Institute for Biomedical Research. Note: Content may be edited for style and length.


Cite This Page:

Whitehead Institute for Biomedical Research. "Study Yields Insights Into Pathogenic Fungi -- And Beer." ScienceDaily. ScienceDaily, 12 August 2005. <www.sciencedaily.com/releases/2005/08/050811105830.htm>.
Whitehead Institute for Biomedical Research. (2005, August 12). Study Yields Insights Into Pathogenic Fungi -- And Beer. ScienceDaily. Retrieved March 28, 2024 from www.sciencedaily.com/releases/2005/08/050811105830.htm
Whitehead Institute for Biomedical Research. "Study Yields Insights Into Pathogenic Fungi -- And Beer." ScienceDaily. www.sciencedaily.com/releases/2005/08/050811105830.htm (accessed March 28, 2024).

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