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M. tuberculosis Rv2252 encodes a diacylglycerol kinase involved in the biosynthesis of phosphatidylinositol mannosides (PIMs)
Author(s) -
Owens Róisín M.,
Hsu Fong Fu,
VanderVen Brian C.,
Purdy Georgiana E.,
Hesteande Elizabeth,
Giannakas Peter,
Sacchettini James C.,
McKinney John D.,
Hill Preston J.,
Belisle John T.,
Butcher Barbara A.,
Pethe Kevin,
Russell David G.
Publication year - 2006
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.1365-2958.2006.05174.x
Subject(s) - phosphatidylinositol , diacylglycerol kinase , biology , biochemistry , kinase , lipoarabinomannan , microbiology and biotechnology , biosynthesis , lipid signaling , mycobacterium tuberculosis , protein kinase c , gene , enzyme , tuberculosis , medicine , pathology
Summary Phosphorylated lipids play important roles in biological systems, not only as structural moieties but also as modulators of cellular function. Phospholipids of pathogenic bacteria are known to play roles both as membrane components and as factors that modulate the infectious process. Mycobacterium tuberculosis is, however, noteworthy in that it has an extremely diverse repertoire of biologically active phosphorylated lipids that, in the absence of a specialized protein translocation system, appear to constitute the main means of communication with the host. Many of these lipids are derived from phosphatidylinositol (PI) that is differentially processed to give rise to phosphatidylinositol mannosides (PIMs) or lipoarabinomannan. In preliminary studies on the lipid processing enzymes associated with the bacterial cell wall, a kinase activity was noted that gave rise to a novel lipid species released by the bacterium. It was determined that this kinase activity was encoded by the ORF Rv2252. Rv2252 demonstrates the capacity to phosphorylate various amphipathic lipids of host and bacterial origin, in particular a M. tuberculosis derived diacylglycerol. Targeted deletion of the rv2252 gene resulted in disruption of the production of certain higher order PIM species, suggesting a role for Rv2252 in the biosynthetic pathway of PI, a PIM precursor.