TB drug discovery: addressing issues of persistence and resistance. Academic Article

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.

authors

• Sacchettini, James

published proceedings

• Tuberculosis (Edinb)

altmetric score

• 3

author list (cited authors)

• Smith, C. V., Sharma, V., & Sacchettini, J. C.

citation count

• 97

complete list of authors

• Smith, Clare V||Sharma, Vivek||Sacchettini, James C

publication date

• January 2004

publisher

• Elsevier  Publisher

published in

• Tuberculosis  Journal

keywords

• Amino Acid Sequence
• Antitubercular Agents
• Drug Design
• Humans
• Molecular Sequence Data
• Mycobacterium Tuberculosis
• Tuberculosis, Multidrug-Resistant

PubMed Central ID

• 14670345

Digital Object Identifier (DOI)

• 10.1016/j.tube.2003.08.019

start page

• 45

end page

• 55

volume

• 84

issue

• 1-2

URL

• http://dx.doi.org/10.1016/j.tube.2003.08.019

user-defined tag

• 3 Good Health and Well-Being