Grant: Operating Grant

The surfaces of bacteria contain a complex and dynamic array of polysaccharides (sugar-containing polymers) that are linked to the surface by a variety of anchoring processes. Cell-surface polysaccharides play diverse functional roles in bacterial pathogens but are generally associated the ability to avoid components of the innate immune system. They are therefore vital for the survival of those bacteria that produce them and influence their ability to cause infection. Polysaccharides are synthesized from building blocks available inside the cell and they must be exported to their final location on the bacterial surface. The goal of this research is a detailed investigation of specific export pathways, as these represent the least understood elements of the polysaccharide-assembly assembly processes. The proposed research addresses fundamental questions concerning how complex molecules pass across biological membranes in a rapid coordinated and specific manner, without compromising the essential barrier functions of the membrane. The exporters are part of a large family called "ABC transporters", whose representatives are found in all forms of life. The two selected prototype systems are relevant for a range of important bacterial pathogens and may also provide insight into related processes in higher organisms. It is conceivable that elucidation of key elements of the export pathways could be exploited for therapeutic intervention strategies. In such a strategy, specifically targeted disruption of polysaccharide export pathways by small molecule inhibitors would yield a bacterium that is easily eradicated by existing host defenses.