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Absolutely, positively searching for new anti-tubercular drugs

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O'Toole, RF and Miller, C and Altaf, M and Bassett, I and Nisa, S and Dempsey, S and Dasysam, N and Earl, E, Absolutely, positively searching for new anti-tubercular drugs, Webster Centre Symposium 2009, 23-24 April, 2009, Dunedin, NZ (2009) [Plenary Presentation]


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Abstract

The most recent data from the World Health Organisation demonstrate that over 9 million new cases of tuberculosis (Tb) occur each year. To meet the WHO’s goal of halving the incidence of the disease, new drugs are needed to treat MDR and XDR forms of Tb, shorten the treatment period and cure latent Tb infections. The primary objective of our work is the identification of new inhibitors of mycobacteria and their cellular targets.

We have developed a fluorescence-based whole cell protocol for the detection of compounds with anti-mycobacterial activity. The assay has been validated for sensitivity and reproducibility using existing first- and second-line anti-tubercular drugs. We have applied the assay to highthroughput screening of multiple synthetic and natural product libraries and have identified a series of previously-unknown mycobacterial inhibitors. To facilitate targeted screens for inhibitors of specific mycobacterial cellular processes or molecules, we have also integrated reverse genetics into our assay. For the detection of compounds which kill non-replicating mycobacteria, we have recently established a metabolism-based high-throughput assay.

The anti-mycobacterial protocols developed and data on the inhibitors identified will be presented. Funding for this work has been provided by the NZ Health Research Council and the Wellington Medical Research Foundation.

Item Details

Item Type:Plenary Presentation
Keywords:Tuberculosis; Drug discovery
Research Division:Medical and Health Sciences
Research Group:Medical Microbiology
Research Field:Medical Bacteriology
Objective Division:Manufacturing
Objective Group:Human Pharmaceutical Products
Objective Field:Human Pharmaceutical Treatments (e.g. Antibiotics)
Author:O'Toole, RF (Dr Ronan O'Toole)
ID Code:106094
Year Published:2009
Deposited By:Medicine (Discipline)
Deposited On:2016-01-28
Last Modified:2016-01-28
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