Sublineages of lineage 4 (Euro-American) Mycobacterium tuberculosis differ in genotypic clustering

Mycobacterium tuberculosis is classified into six phylogenetic lineages, each of which can be divided into sublineages. Sublineages of the same lineage have phenotypic differences, including their capacity to cause disease (pathogenicity).

1) To test the hypothesis that different sublineages of lineage 4, which causes most of the tuberculosis (TB) in the United States, have varying ability to cause secondary cases as determined by genotypic clustering, a proxy for pathogenicity; and 2) to determine if spoligotype and mycobacterial interspersed repetitive units (MIRU) typing could infer sublineage.

We included TB cases caused by lineage 4 strains from our community-based study in San Francisco. Sublineage was determined by regions of difference. Genotypic clustering was determined by insertion sequence 6110 and polymorphic guanine-cytosine-rich sequence. Associations between sublineages and patient characteristics were evaluated with adjusted and unadjusted analyses.

The most frequent sublineage was H37Rv-like. In the adjusted analysis, sublineage 183 was associated with clustering and homelessness. We found that strains from different sublineages had convergent spoligotype and MIRU types.

Sublineage 183 is associated with genotypic clustering, evidence of its being more able to cause secondary cases than the other lineage 4 sublineages. This finding suggests that bacterial factors contribute to the pathogenesis of TB. Spoligotype and MIRU type cannot be used to infer sublineage.