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Researchers identify molecular anchor that allows bacterial invasion of central nervous system

A single molecular anchor that allows bacteria to invade the nervous system may hold the key to treating many types of bacterial meningitis, a University of California, San Diego (UCSD) School of Medicine study has found.

By blocking the molecule's anchoring ability, researchers may be able to find a way to stave off the most common serious infection of the central nervous system and a major cause of childhood death and disability. The researchers' findings appear in the September 2005 issue of the Journal of Clinical Investigation.

Kelly Doran, Ph.D, assistant professor of pediatrics, Victor Nizet, M.D., associate professor of pediatrics, and their colleagues have identified a gene that produces a fat-sugar complex, which in turn anchors a molecule called LTA (short for lipoteichoic acid), found on the bacterial cell wall. This anchoring is a necessary first step for bacteria to cross from the bloodstream into the central nervous system through an anatomical obstacle called the blood-brain barrier.

"Streptococcus, which can cause meningitis, has to penetrate the normally impermeable blood-brain barrier in order to enter the central nervous system and cause disease," said Doran. "How this happens is not well known for bacteria. We wanted to see how bacteria interact with blood-brain barrier cells to begin the process of crossing over into the nervous system."

The team began by looking for new bacterial genes that allowed them to penetrate the barrier. Through a process that involved generating and screening thousands of Streptococcus mutants in a laboratory model of the human blood-brain barrier, the researchers found that a gene called iagA (short for invasion association gene-A) played a central role.

By producing a fat-sugar complex that anchors LTA, iagA establishes a link that allows bacteria to begin making its way into the nervous system. The researchers found that removing the iagA gene from the Streptococcus i
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Contact: Debra Kain
ddkain@ucsd.edu
619-543-6202
University of California - San Diego
1-Sep-2005


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