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Cell wall of pneumonia bacteria can cause brain and heart damage

certain white blood cells. It normally binds to PAFr on the cell lining. The St. Jude team demonstrated that phosphorylcholine, a molecule on the bacteria's cell wall, resembles PAF and exploits this similarity to bind to PAFr.

The researchers demonstrated the role of PAFr by injecting fragments of S. pneumoniae cell wall into normal mice as well as mice that lacked the gene for PAFr (Pafr-/- mice). None of the regular mice survived after eight hours, and cell wall was found in their hearts and brains. However, all of the Pafr-/- mice survived and almost no cell wall was found outside the blood stream. This suggests that PAFr is required for cell walls to escape the bloodstream and enter cardiomyocytes (heart muscle cells) and neurons. Moreover, cell wall fragments lacking phosphorylcholine did not bind to the inner lining of the blood vessels of the animal models, a finding that demonstrates S. pneumoniae cell walls use this molecule to latch onto PAFr.

"S. pneumoniae have learned how to exploit PAFr and use it as a ferry to cross the endothelium of the blood vessels and escape from the bloodstream," Tuomanen said. "From there they enter the cardiomyocytes or neurons in the brain by binding to PAFr on those cells as well."

The investigators used laboratory culture studies to show that while neurons and endothelial cells remained healthy after cell wall uptake, a rapid decline occurred in cardiomyocytes' ability to contract as they do in the heart. The researchers were able to block this effect by first treating the cardiomyocytes with a molecule called CV-6209, which blocked PAFr, preventing the cell wall from binding to it. In fact, mice pretreated for 16 hours with CV-6209 survived, while mice treated after inoculation of cell wall did not.

"Our success in preserving cardiomyocyte function even in the presence of cell wall suggests that it might be possible to safely pre-treat people infected with S. pneumoniae with a drug
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Source:St. Jude Children's Research Hospital


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