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Discovery of Novel Antituberculosis Compounds Using an Intra-Macrophage Assay

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posted on 2021-11-11, 21:48 authored by Murikoli, Rekha Veliyayi

The causative agent of tuberculosis (TB) is Mycobacterium tuberculosis, which affects 2 billion of the world population and kills 1.8 million people annually. It is among the top three infectious killers in the world human immuno deficiency virus, TB and Malaria. Every year among 300-400 new cases of TB are reported in New Zealand according to a recent WHO 2008 report. The current treatment regimen for TB is very long and results in significant toxicity, development of resistant strains and is unable to eliminate the latent bacilli. The above reasons demonstrate the growing need of research for novel antimycobacterial compounds and novel targets for the treatment of TB. Many in vitro and biochemical screens are available for testing against different mycobacterium strains but none of these screens can be considered comprehensive. The reason for this can be the lack of resemblance of the in vitro screen model with the biological systems. Hence we chose the intra-macrophage infection screening model to look for novel antimycobacterial prodrugs which are not active in an in vitro screen but selectively active inside macrophage cell lines. We were successful in establishing and validating such an intra-macrophage infection model using the non-pathogenic M. smegmatis. The model was validated using common anti-tuberculosis drugs. A preliminary high throughput screen was then set up using a mini-library demo model, followed by screening with an actual Lopac synthetic library.

History

Copyright Date

2010-01-01

Date of Award

2010-01-01

Publisher

Te Herenga Waka—Victoria University of Wellington

Rights License

Author Retains Copyright

Degree Discipline

Molecular Microbiology

Degree Grantor

Te Herenga Waka—Victoria University of Wellington

Degree Level

Masters

Degree Name

Master of Science

Victoria University of Wellington Item Type

Awarded Research Masters Thesis

Language

en_NZ

Victoria University of Wellington School

School of Biological Sciences

Advisors

O'Toole, Ronan; Miller, John H