All cells, eukaryotic, archael, or prokaryotic display a diverse array of glycans at their surface. In the case of prokaryotes, these glycans exist as an integral part of a cell wall. The cell wall is thought to have many functions, but one on its most important roles is to provide shape and protection to the cell. Mycobacteria and corynebacteria possess a uniquely thick and hydrophobic cell wall. A prominent feature of the mycobacterial and corynebacterial cell wall is a structurally distinct arabinogalactan (AG) polymer that acts as a scaffold connecting a thick outer layer of mycolic acids to a base layer composed of a cross-linked peptidoglycan network. The arabinan segment of the AG is a complex, branched polysaccharide made entirely of arabinofuranose (Araf) residues. In the case of mycobacteria, this arabinan polysaccharide is essential for survival. The exact function of the arabinan in maintaining mycobacterial viability and parthenogenesis is not known, nor is how the specific structural characteristics of the arabinan contribute to its function. It is hypothesized that synthetic analogues of the Araf donor decaprenylphosphoryl-?-D-arabinofuranose (DPA) could be used to introduce non-natural sugar residues into the cell wall arabinan of living bacteria. The goal of the proposed research is to use synthetic analogues of DPA to probe the structure, function, localization, and dynamics of the arabinan in its native environment.
The arabinogalactan is a structurally distinct polysaccharide that is a prominent feature of the mycobacterial cell wall and is essential for the survival of Mycobacterium tuberculosis. We seek to elucidate the structure function relationships of the arabinogalactan and study its localization and dynamics in the cell wall. These studies will help identify vulnerabilities in the mycobacterial cell wall and guide the design of new drugs to treat mycobacterial infections.