Mycobacterium tuberculosis (Mtb) is a common bacterium that causes tuberculosis, an extremely infectious and deadly disease. Due to improper use of antibiotics, multi-drug resistant Mtb has increased in prominence, creating an urgent need for new treatment options. Trehalose is a glucose disaccharide that is vital to the survival of Mtb and other bacteria, plants, and invertebrates; however, it is not present in mammalian cells. In Mtb, trehalose has many functions, but is primarily used as a vital component in the structure of the cell wall. The enzyme that incorporates trehalose into the mycomembrane, Ag85, has a broad substrate tolerance, allowing it to incorporate synthetically modified trehalose analogs. This inspired us to purse the development of a class of trehalose-based photosensitizers with the potential to target Ag85 for incorporation into the mycomembrane. In this proposal, we present the synthesis and biological evaluation of a small library of trehalose-based photosensitizers using Mycobacterium smegmatis as a model system.

Trehalose-based photosensitizers targeting Mycobacterium tuberculosis

2019 Spring National Meeting

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