TB drug discovery: addressing issues of persistence and resistance | Academic Article individual record
abstract

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.
publication date
2004
publisher
Elsevier bv Publisher
published in
TUBERCULOSIS Journal
keywords
  • Persistence
  • Structure-based Drug Design
  • Tuberculosis
  • Malate Synthase
  • Glyoxylate Shunt
  • Isocitrate Lyase
  • Potential Drug Target
  • Cyclopropane Synthase
  • Mycolic Acid
  • Resistance
altmetric score

3.0

citation count

85

PubMed Central ID
14670345
identifier
74795SE
Digital Object Identifier (DOI)
start page
45
end page
55
volume
84
issue
1-2