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]
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 Type:||Plenary Presentation|
|Keywords:||Tuberculosis; Drug discovery|
|Research Division:||Medical and Health Sciences|
|Research Group:||Medical Microbiology|
|Research Field:||Medical Bacteriology|
|Objective Group:||Human Pharmaceutical Products|
|Objective Field:||Human Pharmaceutical Treatments (e.g. Antibiotics)|
|UTAS Author:||O'Toole, RF (Dr Ronan O'Toole)|
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