Novel targets for tuberculosis drug discovery.
Since the determination of the Mycobacterium tuberculosis genome sequence, various groups have used the genomic information to identify and validate targets as the basis for the development of new anti-tuberculosis agents. Validation might include many components: demonstration of the biochemical activity of the enzyme, determination of its crystal structure in complex with an inhibitor or a substrate, confirmation of essentiality, and the identification of potent growth inhibitors either in vitro or in an infection model. If novel target validation and subsequent inhibition are matched by an improved understanding of disease biology, then new antibiotics could have the potential to shorten the duration of therapy, prevent resistance development and eliminate latent disease.
Mdluli
Khisimuzi
K
Global Alliance for TB Drug Development, 80 Broad Street, 31st Floor, New York, NY 10004, USA. khisi.mdluli@tballiance.org
Spigelman
Melvin
M
D000596:Amino Acids / Q000096:biosynthesis; D000995:Antitubercular Agents / Q000494:pharmacology*; D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism; D004269:DNA, Bacterial / Q000096:biosynthesis; D015195:Drug Design; D005227:Fatty Acids / Q000096:biosynthesis; D005685:Galactans / Q000096:biosynthesis; D007522:Isocitrate Lyase / Q000037:antagonists & inhibitors / Q000235:genetics; D010457:Peptidoglycan / Q000096:biosynthesis
D000596:Amino Acids; D000995:Antitubercular Agents; D004269:DNA, Bacterial; D005227:Fatty Acids; D005685:Galactans; D010457:Peptidoglycan; D007522:Isocitrate Lyase; C005653:arabinogalactan