Streptococcal modification of antibody glycosylation during severe infections

Project: Research


Carbohydrates (glycans) on proteins of the immune system are crucial in regulating the immune response. Antibodies are central proteins in the adaptive immune response against infecting microbes, but can also turn against us in autoimmune diseases. Glycans on IgG antibodies are instrumental in binding to Fc receptors on white blood cells and in complement activation.

We have discovered the first bacterial enzymes that specifically modifies glycans on IgG, and have shown that such enzymes can be used to treat autoimmune diseases in animals and as biotechnological tools. However, very little is know how antibody glycan hydrolyzing enzymes influence antibodies and their functions during bacterial infections. Therefore, we have started to follow antibody glycosylation status in patients with streptococcal infections.

Preliminary data indicates that during severe infections, antibody glycans are hydrolyzed, both locally in infected tissues and in circulation. We now propose to expand these clinical studies on patient with mild to severe streptococcal infections, validate the findings in animal infections models with wild type and enzyme deficient bacteria, do in vitro assays of antibody function, and follow antibody responses and antibody glycosylation status when immunity arises. This could elucidate the role for antibody glycosylation during bacterial infections and how this affects immunity, with implications for treatment of bacterial infections and for vaccine development.
Effective start/end date2018/01/012020/12/31