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March 3, 2011 Volume 32, No. 22

Farmer’s ‘trash tree’ is research team’s disease fighter

INTERDISCIPLINARY RESEARCH

Eastern Red Cedar can fight “superbug”

A “trash tree” with little economic value and the ability to destroy farmland could be the key to fighting a deadly bacterium.

A team of scientists at the University of Missouri has found an antibiotic in the Eastern Red Cedar tree that is effective against methicillin-resistant Staphylococcus aureus, or MRSA, a “superbug” that is resistant to most antibiotics.

Researchers in agroforestry, biochemistry and veterinary pathobiology recently shared their research results with colleagues at the International Conference on Gram-Positive Pathogens in Omaha. Their next step is to discover exactly how the compound works, determine if it has any toxic effects and evaluate other potential disease-fighting compounds isolated from the tree. 

If they are successful, physicians will have a new tool to fight deadly staph infections and Missouri farmers will have a new market for a tree found around the state.

The Eastern Red Cedar (ERC) is one of the most widely distributed American tree species. There are about 500 million of them in Missouri, and their range extends from Kansas to the east coast. Birds spread ERC seeds widely, and it is invasive on farm, forest and pasture land. 

In 2007, Chung-Ho Lin, a research assistant professor in the MU Center for Agroforestry, began studying possible commercial use for ERC. Lin’s specialty is finding novel uses for trees, especially how trees and perennial grasses can safely soak up and break down dangerous agrochemicals and munitions waste in soil.

“I was told to find an entrepreneurial use for this ‘trash tree’ so land owners could put their energy into profiting from them instead of cutting them down,” Lin said. “I thought it was a fun challenge.”

Lin aimed his initial investigation at building on existing research showing anti-bacterial potential of ERC-derived compounds and rumors of its effectiveness as a traditional herbal remedy for acne. Then he developed a series of purification processes to isolate the bioactive compounds.

When Lin’s research began to show results in ERC’s anti-microbial characteristics of the compounds he purified, he shared the data with friends in the College of Veterinary Medicine’s Department of Pathobiology and MU’s Department of Biochemistry. Intrigued, Brian Thompson, department of biochemistry, and George Stewart, professor and department chair of veterinary pathobiology, among others, formed an interdisciplinary team to take Lin’s initial findings and identify and isolate the most promising phytochemicals — biologically active organic chemicals — from ERC tissues.

“It was exciting to tackle the research from three widely different disciplines,” Thompson said.  “We each brought a very different perspective to the research.”

Their tests showed that chemical compounds derived from ERC needles and bark were effective as a topical acne treatment. They also found out that the ERC compounds were a strong anti-microbial agent against a wide range of human bacterial pathogens, including tetanus, botulism, strep throat, Listeria and Salmonella germs, cholera and anthrax. 

Interestingly, it took a relatively small concentration of one ERC compound – just 5 micrograms per milliliter – to be effective against MSRA, the superbug infection that plagues many hospitals.

MRSA is an evolving bacterium that is resistant to most medications. The infection is usually isolated to the skin, but it can spread to vital organs causing toxic shock syndrome and pneumonia, especially in people with weakened immune systems. The incidence of disease caused by MRSA bacteria is increasing worldwide. In 2005, more than 94,000 people developed life-threatening MRSA infections in the United States, according to a Centers for Disease Control report, and nearly 19,000 people died during hospital stays related to these infections.

So far, the MU team has successfully isolated 17 bioactive compounds from the fruit and leaves of the Eastern Red Cedar trees with a few being more effective than others. Stewart cautions that the MU research is still in too early of a stage to speculate how effective an ERC-derived treatment for MRSA would be. 

“We still have to determine how this is working on a molecular level and then assure that it poses no toxicity threats before we consider anything resembling clinical trials,” Stewart said.  “We acknowledge how exciting a potentially new topical or oral treatment for MRSA would be, but we are at least a year away from anything product worthy.”

As if a potential treatment for MRSA was not enough, some of the compounds also initially tested positively as a method to inhibit melanin production in certain mouse-derived melanoma cells. In the test tube, the ERC compound inhibited the cancer cell’s ability to divide, leading to them eventually rupture and die.

Stewart said that any clinical testing could be years in the future and would require the small team to expand and recruit experienced clinical trials experts. 

While this occurs, Lin and his agroforestry colleagues will continue to look at ways to help Missouri land owners utilize their ERC trees as a new Missouri cash crop — his original challenge.

“I’m hopeful that I am fulfilling my mission to develop a new use for the red cedar tree,” Lin said.  “I’m excited about this project.  It’s really been fun.”

— Randy Mertens