Structure-Function Studies of Transporters and Enzymes of the Sialic Acid Scavening- and LPS S ialyation Pathways

Purpose and goal

Antimicrobial resistance poses a major global threat to society. Sialic acids are major cell surface sugars involved in many biological functions. Many pathogenic bacteria use sialic acid as an energy source or incorporate the scavenged sialic acid as the outermost sugar on their surface structures. Incorporation allows them to carry out molecular mimicry, cause sepsis, and survive in biofilms. The catabolic pathway has been shown to be important in GI infections. Our contention is that these pathways provide an ideal set of targets for drugs against these pathogenic bacteria.

Expected results and effects

By combining the expertise from several academic groups, we have structurally and functionally characterised sialic acid transporters and enzymes from several pathogenic bacteria. We have designed sialic acid analogs in silico that has also been synthesised and characterised. We aim to develop inhibitors that will lead to a new class of antimicrobial agents.

Planned approach and implementation

We have characterized the structure and function of several sialic acid transporters and enzymes involved in sialic acid uptake and degradation.