Towards the development of high affinity InhA and KasA inhibitors with activity against drug-resistant strains of Mycobacterium tuberculosis [Elektronische Ressource] = Entwicklung von hoch-affinen InhA- und KasA-Inhibitoren gegen resistente Stämme von Mycobacterium tuberculosis / submitted by Sylvia Rosie Luckner

Towards the development of high affinity InhA and KasA inhibitors with activity against drug-resistant strains of Mycobacterium tuberculosis Entwicklung von hoch-affinen InhA und KasA Inhibitoren gegen resistente Stämme von Mycobacterium tuberculosis Doctoral thesis for a doctoral degree at the Graduate School of Life Sciences, Julius-Maximilians-Universität Würzburg, Section Biomedicine submitted by Sylvia Rosie Luckner from Nürnberg Würzburg 2009 Submitted on: …………………………………………………………..…….. Members of the Promotionskomitee: Chairperson: Michael Sendtner Primary Supervisor: Caroline Kisker Supervisor (Second): Peter Tonge Supervisor (Third): Thomas Müller Date of Public Defence: …………………………………………….………… Date of Receipt of Certificates: ………………………………………………. iiSUMMARY Summary Mycobacterium tuberculosis is the causative agent of tuberculosis and responsible for more than eight million new infections and about two million deaths each year. Novel chemotherapeutics are urgently needed to treat the emerging threat of multi drug resistant and extensively drug resistant strains. Cell wall biosynthesis is a widely used target for chemotherapeutic intervention in bacterial infections. In mycobacteria, the cell wall is comprised of mycolic acids, very long chain fatty acids that provide protection and allow the bacteria to persist in the human macrophage.