Tuberculosis drug targets.
Despite the availability of the BCG vaccine and chemotherapy, tuberculosis (TB) remains a leading infectious killer worldwide. The recent rise of TB and especially the alarming increase of drug-resistant TB call for urgent need to develop new anti-TB drugs. Lengthy chemotherapy and increasing emergence of drug-resistant strains pose a significant problem for effective control. The need for a lengthy TB therapy is a consequence of the presence of persistent Mycobacterium tuberculosis, not effectively killed by current anti-TB agents. A list of new drug candidates along with proposed targets for intervention is described. Recent advances in the knowledge of the biology of the organism and the availability of the genome sequence provide a wide range of novel targets for drug design. Gene products involved in controlling vital aspects of mycobacterial metabolism, persistence, virulence and cell wall synthesis would be attractive targets. It is expected that the application of functional genomics tools, such as microarray and proteomics, in combination with modern approaches, such as structure-based drug design and combinatorial chemistry to biology-based targets, will lead to the development of new drugs that are not only active against drug-resistant TB but also can shorten the course of TB therapy.
Zhang
Ying
Y
Department of Molecular Microbiology and Immunology, Bloomberg, School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. yzhang@jhsph.edu
Amzel
L Mario
LM
D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D024881:Drug Resistance, Bacterial / Q000235:genetics; D006801:Humans; D014376:Tuberculosis / Q000188:drug therapy*
D000995:Antitubercular Agents