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IS 6110 functions as a mobile, monocyte‐activated promoter in Mycobacterium tuberculosis
Author(s) -
Safi Hassan,
Barnes Peter F.,
Lakey David L.,
Shams Homayoun,
Samten Buka,
Vankayalapati Ramakrishna,
Howard Susan T.
Publication year - 2004
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2004.04037.x
Subject(s) - biology , gene , mycobacterium tuberculosis , promoter , transcription (linguistics) , inverted repeat , insertion sequence , microbiology and biotechnology , tuberculosis , downregulation and upregulation , gene expression , genetics , medicine , pathology , transposable element , linguistics , philosophy , genome
Summary The mobile insertion sequence, IS 6110 , is an important marker in tracking of Mycobacterium tuberculosis strains. Here, we demonstrate that IS 6110 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 ≈ 85 bp upstream of the 3′ end of IS 6110 . 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 IS 6110 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 IS 6110 and downstream genes was confirmed by reverse transcription polymerase chain reaction. The ability to activate genes during infection suggests that IS 6110 has the potential to influence growth characteristics of different strains, and indicates another mechanism by which IS 6110 can impact M. tuberculosis evolution.