Abstract:
:The mobile insertion sequence, IS6110, is an important marker in tracking of Mycobacterium tuberculosis strains. Here, we demonstrate that IS6110 can upregulate downstream genes through an outward-directed promoter in its 3' end, thus adding to the significance of this element. Promoter activity was orientation dependent and was localized within a 110 bp fragment adjacent to the right terminal inverted repeat. Transcripts from this promoter, named OP6110, begin approximately 85 bp upstream of the 3' end of IS6110. Use of green fluorescent protein (GFP) expression constructs showed that OP6110 was upregulated in M. tuberculosis during growth in human monocytes and in late growth phases in broth. Analysis of natural insertion sites in M. tuberculosis showed that IS6110 upregulated expression of several downstream genes during growth in human monocytes, including Rv2280 in H37Rv and the PE-PGRS gene, Rv1468c, in the clinical strain 210, which is a member of the Beijing family. Transcription between IS6110 and downstream genes was confirmed by reverse transcription polymerase chain reaction. The ability to activate genes during infection suggests that IS6110 has the potential to influence growth characteristics of different strains, and indicates another mechanism by which IS6110 can impact M. tuberculosis evolution.
journal_name
Mol Microbioljournal_title
Molecular microbiologyauthors
Safi H,Barnes PF,Lakey DL,Shams H,Samten B,Vankayalapati R,Howard STdoi
10.1111/j.1365-2958.2004.04037.xsubject
Has Abstractpub_date
2004-05-01 00:00:00pages
999-1012issue
4eissn
0950-382Xissn
1365-2958pii
MMI4037journal_volume
52pub_type
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