Novel drug target strategies against Mycobacterium tuberculosis.
The resurgence of drug resistant tuberculosis (TB) is a significant global healthcare challenge. Mycobacterium tuberculosis (MTB), TB's causative agent, evades the host immune system and drug regimes by entering prolonged periods of non-proliferation or dormancy. In infected individuals, the immune system sequesters MTB into structures called granulomas where the bacterium survives by shifting into a non-replicative state. Although still not well understood, progress has been made in characterizing the genetic program of MTB, activated by DosR (DevR) signal transduction that allows adaptation to the hypoxic, nutrient limiting granuloma microenvironment. Recent work, especially the identification genes involved in regulatory networks and the Enduring Hypoxic Response (EHR), hold promise for developing new drugs targeting dormancy phase MTB.
Murphy
Dennis J
DJ
Computational Biology, Molecular Discovery Research, GlaxoSmithKline, 1250 South Collegeville Road, UP1345, P.O. Box 5089, Collegeville, PA 19426-0989, USA. Dennis.Murphy2@verizon.net
Brown
James R
JR
D000222:Adaptation, Physiological; D000995:Antitubercular Agents / Q000494:pharmacology*; D006099:Granuloma / Q000382:microbiology; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D015398:Signal Transduction; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy / Q000382:microbiology
D000995:Antitubercular Agents