The causative agent of tuberculosis (TB), Mycobacterium tuberculosis (Mtb), possesses a complex cell envelope decorated with an array of unique glycoconjugates that provide protection to the bacterium and coordinate many of the host–pathogen interactions involved in Mtb pathogenesis. Many of these glycoconjugates, along with their associated metabolic pathways, are essential and mycobacteria-specific, making them highly attractive targets for TB drug, diagnostic, and vaccine development. However, progress in this area is impeded by the lack of tools for studying Mtb glycoconjugates, which ultimately prevents many TB researchers from pursuing fundamental studies and clinical applications related to these structures. Because the glycoconjugates of mycobacteria are structurally and functionally distinct from glycoconjugates in eukaryotes and even other bacteria, the vast majority of tools developed for these systems are not applicable to studying Mtb. The goal of our research program is to develop novel tools that facilitate the investigation of mycobacterial glycoconjugates, and to apply these tools in basic and applied TB research. We develop carbohydrate-based probes that exploit unique carbohydrate metabolic pathways in mycobacteria, which enables labeling and analysis of specific glycoconjugates in intact bacterial cells. This presentation focuses on the design, synthesis, and applications of trehalose-, trehalose monomyoclate-, and trehalose dimycolate-based probes, which are valuable tools for studying virulence-associated glycoconjugates of the unique mycobacterial outer membrane, and which may have future applications as TB diagnostic tools.

Commandeering mycobacterial carbohydrate metabolism for applications in tuberculosis research

255th National Meeting (2018)

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