Sulfate metabolism in M. tuberculosis

Mycobacterial pathogens have been declared a global emergency by the World Health Organization, particularly in regard to the deadly synergy of M. tuberculosis and M. avium with HIV infection. The emergence of multidrug resistant strains of both M. tuberculosis and M. avium has further escalated the need for new therapeutic avenues. M. tuberculosis infection is a complex process that involves residence within lung macrophages, stimulation of an immune response and the formation of granulomas, entry into a latent phase and, ultimately, emergence from latency to produce active tuberculosis. Complex interactions between the pathogen and its host are required to sustain the various stages of the life cycle. In eukaryotes, cell‐cell interactions are often mediated by sulfated metabolites, including glycans, proteins and steroids. A handful of sulfated metabolites have been identified in mycobacteria, including the abundant cell wall glycolipid sulfolipid‐1 (SL‐1) found in M. tuberculosis over 40 years ago. The functions of these metabolites are unknown, but we speculate that they may be involved in cell‐cell communication between host and pathogen. This presentation will focus on our recent progress toward characterizing the functions of sulfated metabolites in mycobacteria and, more broadly, the importance of sulfate metabolic pathways in the survival and pathogenesis of the organism. The long‐term objective is to identify new targets for anti‐mycobacterial therapy, particularly for latent tuberculosis.