NSF Funds Enzyme Study for Possible Cures of Infectious Disease

An Auburn University professor has received a $424,000 National Science Foundation grant for research in the fight against infectious diseases such as malaria, tuberculosis, anthrax, and staph infections.

Evert Duin, an assistant professor of biochemistry in the College of Sciences and Mathematics, is focusing his research on the different steps that biological cells use in making a group of lipids, called isoprenoids. These are fatty substances that are essential for the survival of all organisms including humans.

"The human race is losing its battle against infective bacterial diseases and we are facing new threats from bioterrorism," Duin said. "With some pathogenic bacteria already resistant against four of the five common types of antibiotics, it is important to find new anti-infective drugs that use a completely new and novel way of killing the pathogen."

Such a possibility opened up recently with the discovery that although every organism makes these isoprenoids, a large group of pathogens uses different steps to make these compounds than humans do. Drugs that block the unique steps in these pathogens should in principle kill the pathogens and not have any side effects in humans.

The series of steps in these organisms form what is called the DOXP (1-deoxy-D-xylulose-5-phosphate) pathway. Every step in this pathway is performed by an enzyme.

"The basic idea is to understand how these enzymes convert one compound, the substrate, into another, the product," Duin said. "If we understand how the enzymes do this, we can design and make inhibitors that mimic the original substrate, but contain modifications that cause the enzyme to stall."

Duin said he hopes to make discoveries that work on all harmful organisms, but says finding just one pathway-and-drug combination to combat a specific disease, such as malaria or methicillin-resistant Staphylococcus aureus (MRSA) infections, would be a major advancement worldwide.

Duin is coordinating his work at Auburn with research groups at the University of Illinois and the Medical Center of the Universities of Marburg and Giessen in Germany. If his research is successful, the German groups will conduct clinical studies.

"We think that a successful treatment of a patient now and in the future might ideally rely on a drug combination targeting two or more enzymes of a single pathway," he said. "A drug that blocks only one reaction step might become useless by a mutation in the pathogen."

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