Deciphering the role of IS6110 in a highly transmissible Mycobacterium tuberculosis Beijing strain, GC1237

Abstract

The capacity of infection and the ability of Mycobacterium tuberculosis strains belonging to the Beijing family to spread rapidly probably result from genetic advantages and unidentified mechanisms of virulence not yet thoroughly investigated. Among the mechanisms proposed to be responsible for the varying virulence phenotypes of M. tuberculosis strains we find IS6110 insertions, genetic reorganizations and deletions, which have strong influences on fitness. Beijing family is one of the lineages with the highest number of copies of IS6110. By studying genetic markers characteristic for this lineage, here we have characterized the clinical isolate M. tuberculosis GC1237 strain responsible for important epidemic outbreaks in the Gran Canary Island. We have identified and analyzed each point of insertion of IS6110 using a bacterial artificial chromosome (BAC) library of this strain, in addition to the use of other approximations. Nineteen copies of IS6110 have been localized in GC1237 genome of which, four copies of IS6110 can act as a promoter and we have focused in the characterization of one copy located 31 bp upstream of the essential gene Rv2179c and compared to the reference strain H37Rv.