During pneumococcal infections, levels of a plasma protein called C-reactive protein (CRP) rise dramatically and protect the body from developing pneumonia. For years, it has been assumed that the protective benefits rested with CRP’s ability to bind to a substance present on the cell wall of the pneumonia-causing bacteria Streptococcus pneumonia.
However, a new study at East Tennessee State University’s James H. Quillen College of Medicine is exploring a different mechanism by which CRP works – one that could potentially open the doors for the development of new medications.
The project is being funded by a four-year $1.3 million grant from the National Institutes of Health.
“The initial belief has been that CRP binds to phosphocholine, a substance found in the cell wall of bacteria,” said Dr. Alok Agrawal, ETSU associate professor of Pharmacology. “Bacteria, once decorated with CRP, can then be attacked by the immune system leading to a decrease in the level of bacteria in the blood.”
However, a recent finding in Agrawal’s lab hinted that this particular binding plays no role in the protective functions of CRP.
Agrawal engineered a mutated, or altered, form of CRP incapable of binding to phosphocholine. Using this mutated CRP in animal models, he found that it offered the same protective benefits against pneumococcal infection.
With this new grant project, Agrawal, in collaboration with Dr. Donald A. Ferguson Jr., ETSU associate professor of microbiology, will examine closely the anti-pneumococci action of CRP.
“Our goal is to better understand the mechanisms of anti-microbial actions of CRP,” Agrawal added. “In defining the process by which CRP protects against pneumococcal infections, we will be looking to see how CRP directly or indirectly acts on the bacterial surfaces to kill them. What are the major ‘players’ in the body that cooperate with CRP in making this happen?
“We suspect that CRP doesn’t function the same way in every individual, and it is possible that the mechanisms by which CRP exerts its anti-microbial actions may be ineffective in people who develop pneumonia despite high levels of CRP. Another question deals with the possibility that in vitro-prepared CRP-treated immune cells may be effective in treating microbial infections.”
CRP has been conserved throughout millions of years of evolution. Besides mammals, CRP is also present in insects, birds, fish, and reptiles, suggesting a broad range of defensive functions of CRP. Recent studies from Agrawal’s lab found that CRP also offered anti-atherosclerotic benefits.

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