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The path to new antibiotics
Date:8/27/2009

LA JOLLA, Calif., August 27, 2009 -- Researchers at Burnham Institute for Medical Research (Burnham), University of Texas Southwestern Medical Center and University of Maryland have demonstrated that an enzyme that is essential to many bacteria can be targeted to kill dangerous pathogens. In addition, investigators discovered chemical compounds that can inhibit this enzyme and suppress the growth of pathogenic bacteria. These findings are essential to develop new broad-spectrum antibacterial agents to overcome multidrug resistance. The research was published in the Cell journal Chemistry & Biology on August 27.

Andrei Osterman, Ph.D., an associate professor in Burnham's Bioinformatics and Systems Biology program, and colleagues, targeted the bacterial nicotinate mononucleotide adenylyltransferase (NadD), an essential enzyme for nicotinamide adenine dinculeotide (NAD) biosynthesis. NAD has many crucial functions in nearly all important pathogens and the bacterial NadD differs significantly from the human enzyme.

"It's clear that because of bacterial resistance, we need new, wide-spectrum antibiotics," said Dr. Osterman. "This enzyme is indispensable in many pathogens, so finding ways to inhibit it could give us new options against infection."

According to the National Institutes of Health, drug resistance is making many diseases increasingly difficultand sometimes impossibleto treat. They point to tuberculosis and methicillin-resistant Staphylococcus aureus (MRSA) as two pathogens that pose a serious threat to human health.

Using a structure-based approach, the team searched for low-molecular-weight compounds that would selectively inhibit bacterial NadD, but not the human equivalent, by screening, in silico, more than a million compounds. Experimental testing of the best predicted compounds against Escherichia coli and Bacillus anthracis (anthrax) led them to a handful of versatile inhibitory chem
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Contact: Josh Baxt
jbaxt@burnham.org
858-795-5236
Burnham Institute
Source:Eurekalert

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