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Plant pathologist's work could lead to new drug for humans

STARKVILLE — A Mississippi State University plant pathology researcher’s discovery of an agricultural phenomenon could lead to the development of a new antifungal drug.

The potential drug shows significant promise for the treatment of serious fungal infections in people with compromised immune systems, such as those undergoing chemotherapy treatments and those with HIV or AIDS. While MSU holds numerous patents and licenses, this is the first time a potential pharmaceutical drug has emerged from MSU research.

Dr. Shien Lu, an associate professor in the Department of Biochemistry, Molecular Biology, Entomology and Plant Pathology, was studying crop reactions to plant pathogens. He discovered a patch of disease-suppressive soil in Mississippi, and that led to the identification of the antifungal compound occidiofungin.

“I isolated the bacterial strain MS14 from the root surface of diseased lawn grasses infected by the fungal pathogen Rhizoctonia solani,” Lu said. “We found that the bacteria produce the compound occidiofungin, which shows significant fungicidal activities to various plant and animal fungal pathogens.”

This new compound appears to kill fungus rather than simply suppressing it, as do many of the products currently on the market.

“Occidiofungin has great potential as a novel pharmaceutical drug or as a fungicide for agriculture,” Lu said.

When he found that nothing had yet been published about this antifungal compound, Lu decided to explore it further. The compound quickly became the subject of extensive, ongoing studies to determine its potential as a pharmaceutical drug or fungicide.

“The current studies suggest occidiofungin may disrupt cell wall formation and inhibit some enzyme functions in fungus,” Lu said. “Occidiofungin may have a novel mode of action compared to current antifungal drugs.”

Upcoming clinical evaluations will examine its effects on animal fungal infections and its performance in plant disease applications.

MSU College of Veterinary Medicine adjunct professor and Texas A&M University professor Dr. James Smith explained some of the potential this drug candidate has shown in studies.

“Occidiofungin has been determined to be rapidly fungicidal at therapeutic concentrations and has a broader spectrum of activity than other clinically used antifungals,” Smith said. “It holds great promise for the treatment of serious fungal infections, which can reduce the mortality rate of immuno-compromised patients.”

Josh Jeanson, a licensing associate in MSU’s Office of Technology Commercialization, said MSU filed for a patent on the compound in May 2010. In October 2011, MSU began the process to protect its ownership of this compound in several other countries.

With patents filed on the novel compounds, researchers began the long, slow process of characterizing the compound. Lu and Smith are working on it along with CVM researchers Dr. Frank Austin and Dr. Stephen Pruett.

“They’re looking at what it is, how it works and what it appears to do, as well as what it is effective against, any known dangers associated with it and whether it is safe for humans and animals,” Jeanson said. “This will be an ongoing process for several years, and we hope it will spawn a lot of collaborative research at MSU.”

Working on this project are Lu, who contributed bacterial isolation and identification, genetic analysis of biosynthesis, fungal spectrum of activity studies and mode of action studies; Austin, who contributed to the preclinical toxicology and fungal spectrum of activity studies; Pruett, who contributed to preclinical toxicology studies; Smith, who contributed to antifungal isolation, structural characterization, pharmacodynamics and mechanism of action studies; and Dr. Donna Gordon, MSU assistant professor of biological sciences, who also contributed to the mechanism of action studies.



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