This research project encompasses a number of different approaches to both understand how current antitubercular chemotherapy works using the most modern technologies and to use this information to develop new and improved therapies and therapeutic approaches. Individual projects within this framework are aimed at; (1) understanding the biochemical mode of action of existing front-line antituberculars such as isoniazid, pyrazinamide and ethambutol, (2) understanding the action of various agents in animal models of tuberculosis therapy, and (3) understanding the development of resistance within patients undergoing chemotherapy. The project relies on the development of advanced animal models for predicting drug efficacy under real world conditions. In addition, development of screening assays that would predict drugs able to shorten the current duration of therapy or treat latent infections have been a large focus. Section scientists have also been involved in understanding the mechanism of action of second-line antituberculars and the evolution of multidrug resistance in patients in South Korea and Cambodia. A Natural History clinical research protocol is in the final stages of IRB approval, an IRB has been constituted in South Korea, and GCP training of staff at the clinical research site in South Korea has been completed. In addition, a Phase I clinical trial of pimonidazole, a marker of hypoxic tissues, has been initiated in South Korea and is in the final stages of IRB approval and registration with the Korean FDA.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000734-09
Application #
6986340
Study Section
(LIG)
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2004
Total Cost
Indirect Cost
Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Jeon, Christie Y; Hwang, Soo Hee; Min, Jin Hong et al. (2008) Extensively drug-resistant tuberculosis in South Korea: risk factors and treatment outcomes among patients at a tertiary referral hospital. Clin Infect Dis 46:42-9
Eum, Seok-Yong; Lee, Ye-Jin; Kwak, Hyun-Kyung et al. (2008) Evaluation of the diagnostic utility of a whole-blood interferon-gamma assay for determining the risk of exposure to Mycobacterium tuberculosis in Bacille Calmette-Guerin (BCG)-vaccinated individuals. Diagn Microbiol Infect Dis 61:181-6
Boshoff, Helena I M; Barry 3rd, Clifton E (2005) Tuberculosis - metabolism and respiration in the absence of growth. Nat Rev Microbiol 3:70-80
Boshoff, H I; Barry, C E (2005) A low-carb diet for a high-octane pathogen. Nat Med 11:599-600
Barczak, Amy K; Domenech, Pilar; Boshoff, Helena I M et al. (2005) In vivo phenotypic dominance in mouse mixed infections with Mycobacterium tuberculosis clinical isolates. J Infect Dis 192:600-6
Tsenova, Liana; Ellison, Evette; Harbacheuski, Ryhor et al. (2005) Virulence of selected Mycobacterium tuberculosis clinical isolates in the rabbit model of meningitis is dependent on phenolic glycolipid produced by the bacilli. J Infect Dis 192:98-106
Koshkin, Aleksey; Zhou, Xiao-ti; Kraus, Carl N et al. (2004) Inhibition of Mycobacterium tuberculosis AhpD, an element of the peroxiredoxin defense against oxidative stress. Antimicrob Agents Chemother 48:2424-30
Boshoff, Helena I M; Myers, Timothy G; Copp, Brent R et al. (2004) The transcriptional responses of Mycobacterium tuberculosis to inhibitors of metabolism: novel insights into drug mechanisms of action. J Biol Chem 279:40174-84
Barry 3rd, Clifton E; Boshoff, Helena I M; Dowd, Cynthia S (2004) Prospects for clinical introduction of nitroimidazole antibiotics for the treatment of tuberculosis. Curr Pharm Des 10:3239-62
Thim, Sok; Sath, Sun; Sina, Meas et al. (2004) A community-based tuberculosis program in Cambodia. JAMA 292:566-8

Showing the most recent 10 out of 22 publications