Abstract
Mycobacterium tuberculosis, the causative agent of tuberculosis, is on the rise again in step with the HIV/AIDS pandemic. Characteristically, M. tuberculosis features a hydrophobic cell envelope conferring resistance to degradation by host defences and impeding drug entry. This review focuses on mycolic acids, the distinctive cornerstone lipids of that cell envelope. The structure of these α-alkyl-β-hydroxy fatty acids is discussed along with their relation to pathogenicity. From the uniqueness of their structures and biosynthesis, rationales to target enzyme complexes involved in mycolic acid biosynthesis are discussed. The uniqueness of mycolic acids is also the basis of their application for immunodiagnosis of tuberculosis, an application showing renewed promise. Finally, emerging insights into the role of mycolic acids in the host–pathogen interaction are discussed, ascribing to mycolic acids a function in promoting cellular immune defences but also immune tolerance and the formation of foam macrophages.