Virulence factors of Mycobacterium bovis

Abstract

Virulence factors of Mycobacterium bovis are the special properties that enable it to infect, survive, multiply and cause disease in an animal host. An understanding of these factors will lead to new strategies including an effective vaccine to control bovine tuberculosis. A few factors have already been identified and two broadly different approaches to discover other virulence factors are now being used. In the first approach, libraries of random M. bovis mutants are produced, the likely attenuated mutants are identified using a screening technique and the interrupted genes in selected mutants are identified. In the second approach, genes encoding putative virulence factors are selected by a range of different methods and then inactivated, usually by allelic exchange, to produce likely attenuated mutants of M. bovis. In both approaches, loss of virulence by a mutant must be determined in an animal model. Subsequently, the mutant must be complemented back to virulence with an active form of the identified gene in order to demonstrate that loss of virulence was not due to polar effects of the mutation on nearby genes. It is almost certain that most of the virulence factors of M. bovis are the same as those of the classical human tuberculosis organism, Mycobacterium tuberculosis, as both organisms can cause identical clinical disease in humans and are genetically very similar. Many putative virulence genes are now being investigated and only the inherent slowness with which mycobacterial work proceeds, delays the inevitable arrival of an exciting new phase in the understanding of mycobacterial disease.