Grant: Operating Grant

The surfaces of bacteria are typically composed of a complex and dynamic array of carbohydrate-containing macromolecules. An extensive layer of polysaccharide known as the capsule covers the surfaces of many bacterial pathogens. Capsules have crucial roles in many interactions between bacteria and their environments, including interplay between invading bacteria and host cell defenses. Capsules are generally protective structures and treatments that eliminate capsules (or dramatically reduce their size) can render a bacterial pathogen susceptible to normal host defenses. Consequently, reactions involved in capsule synthesis represent potential targets for therapeutic intervention. Any attempts to develop capsule assembly as a therapeutic target requires a detailed understanding of the underlying processes and this is the goal of our work. We intend to characterize in detail the structure and function of two protein families involved in novel aspects of capsule assembly. The precise mechanisms of action of these proteins are unknown. However, representatives are widely distributed in bacteria, indicating that the results obtained will have broad impact. In addition, the complex processes underlying capsule assembly are of fundamental importance and our studies are expected to provide insight into other important cellular events in pathogenic bacteria.