According to Hardwidge, once bacteria such as C. rodentium and E. coli enter the body, the pathogens use a needle-like secretion apparatus to inject bacterial proteins into intestinal cells. Some of these proteins prevent the innate immune system from fighting the bacterium. One of these injected proteins is NleB.
Hardwidge and colleagues observed that the NleB protein binds with a protein in human cells named GAPDH. NleB modifies the GAPDH protein with a specific sugar molecule and prevents it from participating in a complex biochemical pathway that ultimately allows the innate immune system to respond efficiently to pathogens.
"The function of GAPDH in this pathway was less clear before we did these experiments," Hardwidge said. "GAPDH has well-known functions in the metabolism, but we observed that it also participates in how a cell responds to an infecting bacterium. We're very interested in the fact that this metabolic enzyme has apparently evolved also to be an important part of the innate immune system."
Hardwidge said that E. coli and C. rodentium using the NleB protein to target GAPDH and inhibit innate immunity is also an interesting finding, which will be characterized in greater detail in continuing studies.
With a more advanced understanding about how the innate immune system responds biochemically to invading bacteria -- and how those bacteria suppress the response -- scientists may be able to advance research and therapeutic drug development in other diseases, Hardwidge said. For example, cancers, Crohn's disease and Rheumatoid arthritis all are tied to overactive inflammation. In some cases, the same pathway in which GAPDH participates regulates the inflammation.
"The cell is so complicated, it's amazing that it even works at all, especially when you consider that it is three-dimensional and compartmentalized," Hardwidge said. "We have a general understanding about this important pathway that triggers a defensive response. But when you get into the details of how this pathway is regulated, we're still learning and understanding what exactly is going on. Now, low and behold, there is a new protein involved."
Source: Kansas State University News Service