Genetic Diversity in Mycobacterium tuberculosis

Abstract

Recent years have witnessed an increased appreciation of the extent and relevance of strain-to-strain variation in Mycobacterium tuberculosis. This paradigm shift can largely be attributed to an improved understanding of the global population structure of this organism, and to the realisation that the various members of the M. tuberculosis complex (MTBC) harbour more genetic diversity than previously realised. Moreover, many studies using experimental models of infection have demonstrated that MTBC diversity translates into significant differences in immunogenecity and virulence . However, linking these experimental phenotypes to relevant clinical phenotypes has been difficult, and to date, largely unsuccessful. Nevertheless, emerging high-throughput technologies, in particular next-generation sequencing , offer new opportunities, and have already lead to important new insights. Given the complexity of the host-pathogen interaction in tuberculosis, systems approaches will be key to define the role of MTBC diversity in the fight against one of humankind's most important pathogens.

Origins of a 350-Kilobase Genomic Duplication in Mycobacterium tuberculosis and Its Impact on Virulence

“…Given the apparent rapidity and frequency with which genetic variants appear and establish themselves within in vitro cultures, the potential is clearly there for at least some of the phenotypic variation that has been reported to date, even among isolates of the same lineage, to be a function of in vitro-acquired mutations rather than a product of the original patient isolates themselves. In a similar vein, it also seems reasonable to expect that a portion of the genetic heterogeneity (SNPs and in-dels) that has been reported at the individual strain level (4,(60)(61)(62)(63) also has been derived during in vitro culture, particularly where isolates have been shared and passaged multiple times by multiple laboratories.…”

Mycobacterium tuberculosis: ecology and evolution of a human bacterium

“…Indeed, its airborne transmission is characteristic of a disease transmitted in highpopulation-density areas. In parallel, its capacity to remain latent in humans for several decades, while still evolving, is typical of a disease transmitted in regions with low population density (Gagneux, 2012(Gagneux, , 2013. This feature could be the result of a host-pathogen co-adaptation that might have allowed MTBC survival during the long period when inter-human transmission was rare and sporadic.…”

Multidrug-Resistant Mycobacterium tuberculosis of the Latin American Mediterranean Lineage, Wrongly Identified as Mycobacterium pinnipedii (Spoligotype International Type 863 [SIT863]), Causing Active Tuberculosis in South Brazil

“…M. tuberculosis is the predominant cause of human TB worldwide, but M. africanum and M. bovis remain important agents of human disease in certain geographical regions (9). The MTBC species share identical 16S rRNA sequences, and recent studies have improved our knowledge on the genetic diversity, host range, epidemiological aspects, and differences in pathogenicity and virulence among the species of the complex (10,11). Based on the various genotyping techniques, like spoligotyping (12), restriction fragment length polymorphism (RFLP) (13), mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing (14), and whole-genome sequencing (15), M. tuberculosis strains have been subdivided into lineages and families.…”