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Center of Excellence for Inflammation, Infectious Disease & Immunity

Quillen College of Medicine

Center News

Dr. Alok Argawal Receives NIH R56 Award for Research into C-Reactive Proteins

Pneumococcal pneumonia is a serious disease that affects over 3 million Americans annually. This disease is especially dangerous for the very young and the elderly. While some strains can be treated with antibiotics and others can be prevented with vaccines, many strains remain highly resistant to treatment.

There are currently 90 strains of Streptococcus pneumoniae (pneumococcus) of which only 27 have a proven vaccine. These vaccines work by identifying the polysaccharides, or sugars, present on the bacterial cell surface. The composition of these sugars change as the strains mutate.  Due to the ease that these strains change, the currently available vaccines will become a less and less relevant treatment option.

While we may still be figuring out how to treat these resistant strains, we have a good idea why they are so resistant. Pneumococci have a mechanism that allows them to hide from our immune system. Surviving bacteria disguise themselves by taking a protein from our blood and covering their outer membrane with it. This makes it impossible for our immune systems to differentiate between a host cell and a foreign bacterial cell.

We have to be smarter than bacteria, says Dr. Alok Agrawal, a professor in the department of Biomedical Sciences at East Tennessee State University. Dr. Agrawal has recently received an R56 Grant Award from NIH to test a new method to outsmart one species of bacteria responsible for pneumococcal infections.

Dr. Agrawal teaching

c reactive protein

 

C-reactive protein (CRP) is a component of our innate immune system. They act as an identifier of pathogenic cells in our body. CRP identifies pneumococci by the presence of specific complex carbohydrate molecule present on the surface and then activates the other components of the immune system to kill the bacteria. However, if a bacterium has recruited a host protein on its surface, then even if CRP recognizes the bacterium, it cant activate the other component of the immune system to kill the bacterium. He also thinks that CRP molecules change their structure at certain locations in the body and that modified CRP can kill pneumococci even if they have recruited the host protein on the surface. In certain peoples body, CRP molecules are unable to change their structure due to inappropriate inflammation and therefore unable to kill the bacteria, resulting in the disease.

Dr. Agrawal thinks that CRP can be genetically engineered to facilitate the killing those bacteria which disguise as host cells, regardless of the strain of the bacteria. Instead of targeting the polysaccharides that vary by strain of pneumococci, this proposed treatment attaches to the host protein that is recruited by all strains. This technique could end the need for a different vaccine for each strain of the disease and further limit the use of antibiotics as a treatment mechanism in pneumonia cases.

This work represents a proof of principle for a new treatment method that may be used against other infectious diseases as well. CRP based treatment has the potential to be safer and with fewer side-effects than typical antibiotic regimens. CRP can also be designed to target specific pathogenic cells trying to evade the bodys immune system while ignoring all other cells in the body. Says Dr. Agrawal, We dont really know if all bacteria hide like this one, but this gives us a new line of investigation into how all bacteria might work.

Dr. Agrawal will continue his research on this fascinating subject thanks to a grant award from the National Institute of Health (NIH) ($370K for one year). He has received an R56 award that will continue his research for the next one year. Dr. Agrawal will work on this project with his collaborator, Dr. Michael Kruppa, an associate professor in the same department. This grant will allow Agrawal and his team to test lab-made modified CRP molecules in an animal model of pneumococcal infection.

 

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