Cunnion, Kenji Mason
Hyperglycemic effects on complement-mediated host defenses against Staphylococcus aureus in an animal model.
General Research Subject: Both Type 1 And Type 2 Diabetes
Type of Grant: Innovation
Project Start Date: July 1, 2011
Project End Date: June 30, 2013
Twenty percent of the 23.6 million diabetics in the U.S. will experience foot or leg infections contributing to 71,000 amputations each year. The bacteria Staphylococcus aureus causes the vast majority of foot infections in diabetics and causes other severe infections like bacteremia in intensive care settings. A completely new observation has been made that a vital part of host defenses against infections, the complement system, remains unactivated by Staph aureus in high glucose. This suggests that high glucose in diabetics may prevent this critical host defense from functioning properly in protection against Staph aureus and may be a major reason contributing to diabetic foot infections. These studies propose to understand how this new phenomenon affects the over all immune response to and killing of Staph aureus in a rat model of abdominal infection. This model is ideal in that it will allow an extremely detailed evaluation of how elevated glucose affects the ability of this important host defense to control Staph aureus infection.
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
This project will investigate how diabetes increases the risk of infection by inhibiting a critical area of host defense against infection - the complement system. The complement system is vital for the prevention of bacterial and fungal infections, especially Staphylococcus aureus. S. aureus are the most common bacteria to cause diabetic foot infections and diabetes increases the risk of death if these bacteria enter the blood stream. Our preliminary data from bench-top experiments show that in elevated levels of glucose, which are consistent with mild to moderate hyperglycemia, the central component of the complement system (C3) is inhibited from activating. This, in turn, prevents several critical areas of host defense from functioning properly to fight and kill these bacteria. We have also analyzed the C3 molecule and shown that its structure is altered in elevated glucose compared with normal glucose concentrations.
This project will provide important new insights into why elevated glucose concentrations increase the risk of infection leading to foot infections, amputations, and even death from overwhelming infections.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
Our project will provide important new insights about how elevated glucose increases the risk of infections. This work will hopefully lead to improved and new management strategies for the prevention and treatment of diabetic foot infections and decrease the numbers of limb amputations among diabetic patients.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
Infections, especially diabetic foot infections, have a huge negative
impact on the lives of diabetic patients. As an Infectious Diseases
physician, the potential to decrease the incidence of the infections and
more effectively treat them has tremendous appeal. As a basic science
immunology researcher, I am greatly interested in the effects of
hyperglycemia on complement system and in particular its interaction
with S. aureus.
This award will open a new direction for our research efforts, expanding our investigations of complement host defenses and S. aureus into the vitally important area of diabetic infections. This new direction will enhance our ongoing research efforts and further increase the clinical importance.
In what direction do you see the future of diabetes research going?
The future of diabetes research will be increasing multidisciplinary,
because diabetes affects so many different body functions and organ
systems. One of the most important and fascinating areas is the
interaction of diabetes and the immune system, including the impact of
inflammation. Our work will expand diabetes research into examining its
impact on a new area of the immune system, the complement system,
increasing our understanding of diabetes, host defense, and microbiology
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