TB drug discovery: addressing issues of persistence and resistance.
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Tuberculosis remains a leading cause of mortality worldwide into the 21st century. Among the main obstacles to the global control of the disease are emerging multi-drug resistant strains and the recalcitrance of persistent infections to treatment with conventional anti-TB drugs. Here we review recent developments in our understanding of some of the pathways involved in a persistent infection and pathogenesis of Mycobacterium tuberculosis, which reveal new targets for drug development. We describe the high-resolution crystal structures of enzymes of the glyoxylate shunt, isocitrate lyase and malate synthase, and of the cyclopropane synthases of mycolic acid biosynthesis. Structure-based drug design is now underway with the potential to lead to the development of new anti-tuberculars effective against persistent and resistant Mycobacterium tuberculosis infections.
author list (cited authors)
Smith, C. V., Sharma, V., & Sacchettini, J. C.
complete list of authors
Smith, Clare V||Sharma, Vivek||Sacchettini, James C