Mycobacterium bovis lipids: Virulence and vaccines

Mycobacterium bovis is an important pathogen of both domesticated and wild animals in many countries, and improved vaccines have great potential to assist in its control and eventual eradication. One of the hallmarks of members of the Mycobacterium tuberculosis complex, which includes both M. bovis and M. tuberculosis, is their ability to synthesise an impressive array of unique and complex lipids, many of which act as defensive, offensive or adaptive effectors of virulence. For example, studies focussed on the development of rationally attenuated strains of both M. bovis and M. tuberculosis with efficacy as animal or human vaccines have shown that the phthiocerol dimycocerosates (PDIMs) and glycosylphenol-PDIM (phenolic glycolipid, PGL) are key virulence factors. The availability of the genome sequences for M. bovis and M. tuberculosis, together with mutants of these organisms carrying defects in lipid biosynthesis, and biochemical and molecular tools to dissect lipid biosynthesis pathways, has enabled developments in our understanding of the biosynthesis of PDIMs and PGL, as well as the possible roles played by PDIMs and PGL in virulence. In this article we review some of these developments, and also propose a cryptic lipid biosynthesis pathway in M. bovis and M. tuberculosis that may be involved in the production of an unrecognised, virulence-associated lipopeptide.