A specific protein on the surface of a common bacterial pathogen allows the bacteria to leave the bloodstream and enter the brain, initiating the deadly infection known as meningitis. The new finding, which may guide development of improved vaccines to protect those most vulnerable, including young infants and the elderly, is now available online in the Journal of Experimental Medicine.
"Streptococcus pneumoniae, commonly known as pneumococcus, is responsible for half the cases of bacterial meningitis in humans," said the study's senior author, Victor Nizet, MD, professor of pediatrics and pharmacy at the University of California, San Diego's School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences. "As many as 30 percent of patients can die from this rapidly progressing infection, while half of survivors may be left with permanent neurological problems including deafness, seizures, intellectual deficits or motor disabilities."
Meningitis develops when bacteria penetrate the "blood-brain barrier." Comprised of a single layer of highly specialized microvascular endothelial cells, the blood-brain barrier prevents most large molecules from entering into the cerebrospinal fluid, preserving an optimal biochemical environment for brain function.
The UC San Diego team investigated the functions of a protein known as NanA in order to discover how an entire bacterium can breech the blood-brain barrier and gain access to the central nervous system. NanA is produced by all strains of pneumococcus and displayed prominently on the bacteria's outer surface.
Through genetic manipulations, the researchers were able to remove the entire NanA protein, or just specific sections of the molecule, from the pathogen. They found that while normal pneumococci were able to bind, enter and penetrate through human brain microvascular endothelial cells, mutant bacteria lacking the Na
|Contact: Debra Kain|
University of California - San Diego