Title page for ETD etd-07012005-094850


Document Type Doctoral Thesis
Author Siko, Dismore Gilbert Ramathudi
URN etd-07012005-094850
Document Title Mycobacterial mycolic acids as immunoregulatory lipid antigens in the resistance to tuberculosis
Degree DPhil (Biochemistry)
Department Biochemistry
Supervisor
Advisor Name Title
Prof J A Verschoor Committee Chair
Prof E Johannsen Committee Co-Chair
Keywords
  • Tuberculosis Chemotherapy
  • Host-parasite relationships research
  • Tuberculosis microbiology
Date 2003-04-01
Availability unrestricted
Abstract
Tuberculosis has returned with vengeance mainly due to the resurgence of multi drug resistant strains incurred by non-compliance to the 6-9 months chemotherapy programme. Co-infection with HIV, which disorientates the immune response, has aggravated the situation. This study was built on previous observations that indicated that the major lipid cell wall component of M. tuberculosis, i.e. mycolic acids, a wax that envelopes and protects the bacillus from the hostile host immune system, can be purified and administered to animals for protection against subsequent tuberculosis induction. It was established in this study that mycolic acids pre-treatment can significantly protect mice upon subsequent intranasal infection with M. tuberculosis and that this protection is not attributed so much to the T helper cell immunity, but rather through induction of innate immunity. In the murine AIDS model, innate immunity induced by mycolic acids pre-treatment was not enough to protect the virally immunocompromised mice against subsequent M. tuberculosis infection. Mycolic acids administration in mice did not support tuberculosis chemotherapy to enable shortening of the duration of chemotherapy. In human tuberculosis patients, antibodies to mycolic acids could be measured in a specially adapted configuration of a resonant mirror biosensor. The preliminary investigation opened up the possibility that the prevalence of anti-mycolic acids antibodies in tuberculosis patients may be measured as a surrogate marker for tuberculosis infection. An apparent cross-reactivity between mycolic acids and cholesterol in binding to tuberculosis patient antibodies may provide far reaching insight in the role of the mycolic acids in the cell wall to facilitate infection. This research contributed significantly to the understanding of the host-pathogen interaction in tuberculosis, to open up fresh approaches to improved diagnosis and chemotherapy.

2002 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria.

Please cite as follows:

Siko, DGR 2002, Mycobacterial mycolic acids as immunoregulatory lipid antigens in the resistance to tuberculosis, DPhil thesis, University of Pretoria, Pretoria, viewed yymmdd < http://upetd.up.ac.za/thesis/available/etd-07012005-094850/ >

H834/ag

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