Understanding the genetic diversity of M. tuberculosis
Only 5-10 % of immunocompetent individuals develop TB after being infected with MTB bacteria. The virulence of the infecting strain and host genetic factors are responsible for the differences in infection levels in individuals. Mycobacterial strains of the W-Beijing family have received considerable attention due to their high morbidity and mortality as well as resistance to antimicrobial drugs. These strains originated in the Beijing region in China and have been reported to inhibit host immune responses through the expression of a phenolic glycolipid. Their ability to spread locally probably reflects the high level of fitness of the W-Beijing mycobacterial strains and is due to unidentified virulence factors. The EU-funded TB-VIR project members intend to unveil the genetic determinants causing high virulence in these strains. Scientists elucidated the genetic diversity of the W-Beijing strains by single nucleotide polymorphism (SNP) genotyping analysis and differentiated them on the basis of successively acquired point mutations. Functional screening of an MTB mutant library was used to identify virulent genes in the W-Beijing strains as well as genes required for the infection of macrophages. TB-VIR members also undertook comparative analysis of changes in host cell gene expression following infection with W-Beijing mycobacterial strains and with strains of other genotypes. Host immune responses to the W-Beijing strains and other genotypes were studied to understand the genotype–phenotype relationships and bacteria–host interactions. Given that the global incidence of TB increases by 2 % every year, TB-VIR efforts provided invaluable information on the role of the genetic diversity of MTB in disease development. By understanding the epidemiological success of certain MTB strains, the consortium hopes to design new measures of disease control alongside novel diagnostic tools.
