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Winemaking 'Waste' Fights Disease-Causing Bacteria

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Winemaking waste proves effective against disease-causing bacteria in

early studies

Potential source of next-generation drugs against oral disease: Pinot noir

A class of chemicals in red wine grapes may significantly reduce the

ability of bacteria to cause cavities, according to a study published

recently in the Journal of Agricultural and Food Chemistry. The

findings suggest that specific polyphenols, present in large amounts

in fermented seeds and skins cast away after grapes are pressed,

interfere with the ability of bacteria to contribute to tooth decay.

Beyond cavities, the action of the wine grape-based chemicals may also

hold clues for new ways to lessen the ability of bacteria to cause

life-threatening, systemic infections.

Even better, the compounds embody an emerging philosophy in design of

drugs against bacteria: take away their ability to cause disease

without killing them. Current antibiotics often kill a strain of

bacteria responsible for disease, only to create a vacuum quickly

filled by related strains. The widespread overprescribing of

antibiotics and the speed of bacterial evolution have greatly

increased the likelihood that the strains most able to resist

antibiotics will thrive and spread. This trend is evident in recent

reports that one strain of bacteria has become resistant to all 18

antibiotics approved for use in childhood ear infections, while

another now causes more U.S. deaths than AIDS. New approaches seek to

take away bacterial capabilities that cause disease (virulence

factors) without " selecting for " resistance or killing beneficial

bacteria.

" Most foods contain compounds that are both good and bad for dental

health, so the message is not `drink more wine to fight bacteria,' "

said Hyun Koo, DDS, Ph.D., assistant professor of Dentistry within the

Eastman Department of Dentistry and Center for Oral Biology at the

Medical Center. " We hope to isolate the key compounds within the

winemaking waste that render bad bacteria harmless, perhaps in the

mouth with a new kind of rinse, " said Koo, an author of the current

study.

The findings are the result of collaboration between the University of

Rochester Medical Center and the New York State Agricultural

Experiment Station at Cornell University. Both institutions, with

access to Finger Lakes wineries, have been looking at how compounds

found in wine grapes impact human oral health. Together, they won a

U.S. Department of Agriculture (USDA) grant in December 2005 to study

the influence of grape polyphenols on oral bacteria, and today's

publication is an early result.

Along with the potential value for medicine, the discovery that the

waste products of winemaking may be useful in drug-making has economic

implications. Grapes are one of the world's largest fruit crops, with

more than 80 percent of grapes used to make wine. Fermented winemaking

waste, called pomace, contains at least as many polyphenols as whole

fruit, eliminating the need to use up perfectly good food to make any

future drugs. Accordingly, the USDA is especially interested in the

idea of bioprospecting in the winery versus the rainforest.

Study Details

Koo, who conducts his research at the Eastman Dental Center, concluded

early in his career as an oral biologist that there are biochemical

implications of foods on oral health – other than to say " sugar is bad

for teeth. " In recent years, his and other labs have examined whether

chemicals from cranberries, cocoa and grapes for instance have a

therapeutic effect on bacterial pathogens. All contain polyphenols and

the race is on to determine which may be the most useful medically.

The goal of the current study was to examine the make-up of

polyphenols in red wine grape varieties and their ability to interfere

with Streptococcus mutans (S. mutans), the bacteria that produces the

substances most responsible for tooth decay: acid and the building

blocks (glucans) of a dental biofilm called plaque.

Researchers prepared polyphenolic extracts from harvest season 2005

red wine grape varieties and pomace from wineries in the Finger Lakes

region of New York state. These included Pinot Noir from Hosmer Winery

in Ovid, N.Y., Cabernet Franc from Cornell Orchards in Lansing, N.Y.,

Baco Noir from Pleasant Valley Winery in Hammondsport, N.Y. and

NoiretTM from Swedish Hill Winery in Romulus, N.Y. Varieties were

pre-screened for their phenolic content, and grape pomace was chosen

in general for its ready supply as an inexpensive source material. Red

grapes have been shown to contain 40 percent more phenols content than

white.

The team was most interested in examining the impact of grape

polyphenols on two capabilities of S. mutans that enable it to thrive

in the human mouth. First, it secretes enzymes known as

glucosyltransferases (GTFs) that produce sugary, glue-like substances

(glucans) that firmly attach bacteria to tooth surfaces and form a

tough barrier around bacterial colonies. Such barriers, called the

extracellular polysaccharide (EPS) matrix, protect the colony against

environmental assaults, and make them, in some cases, hundreds of

times more resistant to antibiotics. Bacteria living in these gunky

fortresses are known as biofilms, whether they occur on teeth or

elsewhere in the body. Many Streptococci (strep) and Staphylococci

(staph) cause resistant forms of meningitis, pneumonia, staph aureus,

as well as infections on heart valves and around stents, by forming

biofilms. GTFs are a main virulence factor responsible for S. mutans

biofilm formation, but other pathogens use similar mechanisms to

produce EPS matrix. The hope is that learning about one will suggest

ways to interfere with many.

A second linked set of virulence factors for S. mutans are its

abilities to secrete acid, and to survive in that acid. Having evolved

to be " acid durable, " S. mutans can survive and out-compete other

bacteria in the mouth. Better understanding of these mechanisms could

also yield new ways to fight other biofilm related infections.

In the current study, researchers found that all polyphenol extracts

inhibited two bacterial GTFs by as much as 85 percent (P<0.01)), a

level of inhibition not previously observed in Koo's lab. Cabernet

Franc extracts were more effective GTF inhibitors, with Pinot noir a

close second at concentrations that might be useful therapeutically.

Grape polyphenols were also found to cause S. mutans to produce

significantly less acid. This may be because they inhibit glycolysis,

the process by which the bacteria turns sugar into energy also

produces acid, researchers said. None of the extracts from any variety

killed the bacteria outright. By targeting the ability of S. mutans to

form EPS matrix, for example, therapeutic approaches to reducing the

formation of biofilms could be precise and selective. Further chemical

analysis will be needed to pinpoint which the most effective

polythenol mix.

" Overall, the phenolic extracts disrupt essential virulence traits for

a widespread, destructive oral pathogen, but without killing it, " said

Olga I. Padilla-Zakour, Ph.D., associate professor of Food Processing

within the New York Agricultural Experiment Station of Cornell

University. " We are excited about the potential application of active

compounds from wine grape by-products in the control of biofilms as

part of the precise targeting of bacterial disease. "

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