Drug targets in mycobacterial sulfur metabolism.
The identification of new antibacterial targets is urgently needed to address multidrug resistant and latent tuberculosis infection. Sulfur metabolic pathways are essential for survival and the expression of virulence in many pathogenic bacteria, including Mycobacterium tuberculosis. In addition, microbial sulfur metabolic pathways are largely absent in humans and therefore, represent unique targets for therapeutic intervention. In this review, we summarize our current understanding of the enzymes associated with the production of sulfated and reduced sulfur-containing metabolites in Mycobacteria. Small molecule inhibitors of these catalysts represent valuable chemical tools that can be used to investigate the role of sulfur metabolism throughout the Mycobacterial lifecycle and may also represent new leads for drug development. In this light, we also summarize recent progress in the development of inhibitors of sulfur metabolism enzymes.
Bhave
Devayani P
DP
Chemical Biology Ph.D. Program, University of Michigan, Ann Arbor, Michigan, 48109-2216, USA.
Muse
Wilson B
WB
Carroll
Kate S
KS
D000995:Antitubercular Agents / Q000494:pharmacology*; D001692:Biological Transport; D003545:Cysteine / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006020:Glycopeptides / Q000378:metabolism; D007294:Inositol / Q000378:metabolism; D008715:Methionine / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000378:metabolism*; D019255:NADPH Oxidases / Q000502:physiology; D013431:Sulfates / Q000378:metabolism; D015238:Sulfotransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D013455:Sulfur / Q000378:metabolism*
D000995:Antitubercular Agents; D006020:Glycopeptides; D013431:Sulfates; C089265:mycothiol; D007294:Inositol; D013455:Sulfur; D008715:Methionine; D019255:NADPH Oxidases; D015238:Sulfotransferases; D005978:Glutathione; D003545:Cysteine