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

Grupo de Genética de Micobacterias, Departamento de Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza, Spain.
Tuberculosis (Edinburgh, Scotland) (Impact Factor: 2.71). 03/2011; 91(2):117-26. DOI: 10.1016/
Source: PubMed


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.

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Available from: Isabel Otal, Feb 06, 2014
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    • "In the framework of an ongoing project on structural and functional properties of mycobacterial cell wall components (Correale et al., 2013; Squeglia et al., 2013), we show here that deletion of a single gene in the genome of Mycobacterium marinum (MMAR_3223), a widely used model organism for M. tuberculosis (Bouley et al., 2001; Broussard and Ennis, 2007), affects mycobacterial cell surface properties in vitro and virulence in vivo in the zebrafish model. MMAR_3223 has been shown to be upregulated inside granulomas during long-term frog infection by M. marinum (Chan et al., 2002), whereas its ortholog in M. tuberculosis, rv2179c, is essential for mycobacterial growth (Sassetti et al., 2003) and upregulated in the hyper virulent Beijing strains of M. tuberculosis during macrophage infections (Alonso et al., 2011). However, the exact role played by this gene in mycobacterial pathogenicity is hitherto unknown. "
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    • "On the other hand unique locations were observed in papA4 and Rv2957 genes (N4 strain), interrupting mez and PPE49 genes (CAM22 strain) and in the intergenic region of Rv1542c:Rv1543 (W4 strain) (Additional file 1: Table S5). We corroborated the uniqueness of these sites, after analyzing the literature [10,11,13,16-18,20,22-24,27-35], as was the case for the copy located upstream of Rv2180c gene in GC1237 [10] (Figure 1 and Figure 2). The data suggests that although IS6110 has preferential genomic regions, its insertion is sufficiently random that could generate differences among strains of the same family. "
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