The clinical consequences of strain diversity in Mycobacterium tuberculosis

The influence of strain variation on the outcome of infection with Mycobacterium tuberculosis is an emerging area of research. Significant genetic diversity is generated within the species through deletion, duplication and recombination events; however, unlike many bacterial pathogens gene exchange is rare in M. tuberculosis, resulting in the evolution of distinct clonal lineages. One such lineage, W-Beijing, is particularly virulent in animal models, may be emerging worldwide, has distinct phenotypic and genotypic characteristics and is associated with extrapulmonary disease and drug resistance. Strains of M. tuberculosis responsible for outbreaks have been shown to vary in virulence in animal models, which in turn has been related to their ability to inhibit innate immune responses. However, there is no clear evidence that this variability manifests as differences in human disease. An improved understanding of the phylogenetic relationship between strains of M. tuberculosis, based on increased availability of sequence data from the major strain lineages, will allow a structured approach to understand further the consequences of strain diversity in M. tuberculosis.