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Research Programmes - Tuberculosis

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  • Novel antibiotics by rational drug design

    4th May 2012

    Novel antibiotics by rational drug design

    The discovery of new antibiotic drugs is based on the isolation of compounds that are screened for bacteriocidal or bacteriostatic activity. These compounds may either be chemically synthesised or isolated from nature. An additional route to drug discovery is rational drug design.

    Protein structural analysis, active site modification and reaction mechanism studies performed at the CSIR have identified an enzyme as a potential new drug target for the disease. Structural analysis of reaction intermediates has identified novel molecules as potential drug candidates with application to tuberculosis, as well as other bacterially induced diseases.

    The innovative research and development phase of the project will comprise further structural analysis and molecular modelling of the drug candidates and enzyme, synthesis of the potential drug analogs followed by in vitro enzymatic analysis of efficacy. An analysis of efficacy against growth and the infection process of the pathogen responsible for the disease (Mycobacterium tuberculosis) will also be undertaken.

    This project is being undertaken in collaboration with a number of partners in South Africa, with funding from the Innovation Fund.

    For more information, contact:
    Dr Colin Kenyon, Tel: +27 11 605 2702, Fax: +27 11 608 3020 or
    Prof Jan Verschoor, Tel: +27 12 420 2477 Fax: +27 12 362 5302

  • UP Tuberculosis Research Programme

    4th May 2012

    In 1994 Prof Jan Verschoor of the University of Pretoria (UP), partnered by Adcock Ingram Limited, initiated the tuberculosis (TB) research programme in the Department of Biochemistry at the University. The South African Medical Research Council, THRIP and the National Research Foundation support this tuberculosis research programme.

    In 2001, in collaboration with the Heinrich Heine University in Düsseldorf, Germany, a research paper appeared describing the purification of lipid cell wall antigens from the tuberculosis organism and the effects these have on cells of the human immune system.

    In 2000 Dr Annemieke ten Bokum, a post-doctoral fellow from the EUR, joined the project, contributing towards understanding the arthritis-type auto-immunity associated with tuberculosis. Dr ten Bokum is also a co-inventor, with Prof Verschoor, of a new approach to the therapy of multi-drug resistant tuberculosis, especially with concurrent HIV infection. The University of Pretoria has filed a provisional patent for this in South Africa, while Dr Chris Parkinson of the CSIR in South Africa has synthetised a first prototype version of the patented principle, which is currently undergoing laboratory testing at UP. Work is currently underway to prove the basic concepts of the patent. This patent is the fourth emanating from this project with the UP tuberculosis research team members as inventors and co-inventors. The previous three patents have been filed internationally in the name of Adcock Ingram Limited.

    This resulted in a PhD and MSc at the Universities of Brussels and Gent in Belgium for Dr (MD) Anton Stoltz and Hannelie Korf respectively. They discovered unique morphological and functional changes that the cell wall biolipids of the tuberculosis bacillus brings about in the macrophage target cells of experimental animals. Prof Verschoor, Dr Gilbert Siko and Mr Pieter Vrey visited the Department of Immunology at the Erasmus University Rotterdam (EUR) in The Netherlands to make the resonant mirror biosensor technology applicable to the measurement of biolipids-antibody interaction in tuberculosis.

    The purchase in 2001 of a resonant mirror biosensor and multi-well fluorimeter, equally funded by the CSIR and UP, equipped the Department of Biochemistry with access to the latest technology to study quantitative molecular binding interactions in bio-medical research. This instrument proved to be essential to understand the peculiar interaction of patient antibodies to lipid antigens of the tuberculosis bacillus. This work may provide the solution to serodiagnosis of tuberculosis patients, which would contribute hugely to the management of the tuberculosis epidemic.

    In 2002 Miss Yvonne Vermaak, a MSc student at UP, and Dr Gunther Schleicher, collaborator and post-graduate medical student from the WITS Medical School in South Africa, published their noteworthy results on the study of tuberculosis patient antibodies against cell wall biolipids as possible surrogate markers for tuberculosis infection.

    For more information, contact Prof Jan Verschoor, Tel: +27 12 420 2477, Fax: +27 12 362 5302