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How meningitis bacteria attack the brain
Date:8/18/2009

nA protein or those expressing only a truncated version of the protein largely lost these abilities. Conversely, when the full-length pneumococcal NanA protein was cloned and expressed on the surface of a nonpathogenic laboratory strain, the transformed bacteria gained the ability to bind and enter the same endothelial cells.

"Our tissue culture studies showed that the NanA protein was both necessary and sufficient for bacterial penetration of the blood brain barrier endothelial cells," said Satoshi Uchiyama, MD, a postdoctoral fellow in the Nizet Laboratory and lead author on the study. "After infecting mice intravenously, we also found that far fewer NanA-deficient bacteria left the bloodstream and entered the brain, in comparison to mice infected with the normal pneumococcus."

NanA is best known as an enzyme that cleaves and releases the sugar molecule known as sialic acid, which is present in abundance on the surface of all human cells. While this enzymatic activity played a small part in promoting NanA-mediated blood-brain barrier interactions, a much stronger role was identified for the outer tip of the protein. This tip seems to directly attach to the brain microvascular endothelial cells and then stimulate them to take in the pneumococcus.

"Antibodies directed against the NanA protein also strongly inhibited the ability of pneumococcus to attach to and invade the blood-brain barrier cells," said Kelly Doran, PhD, an assistant professor at both UC San Diego School of Medicine and San Diego State University, who jointly supervised the project with Nizet.

Because NanA is expressed on the surface of all pneumococcal strains, it is an attractive candidate to include in a universal protein-based vaccine against pneumococcal infection according to Nizet, who is also on the medical staff of Rady Children's Hospital, San Diego. Currently, infants and the elderly are immunized with vaccines comprised of surface capsule sugar
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Contact: Debra Kain
ddkain@ucsd.edu
619-543-6163
University of California - San Diego
Source:Eurekalert

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