The interplay between classical and alternative isoprenoid biosynthesis controls gamma delta T cell bioactivity of Listeria monocytogenes

Isoprenoids are synthesised either through the classical, mevalonate pathway, or the alternative, non-mevalonate, 2-C-methyl-erythritol 4-phosphate (MEP) pathway. The latter is found in many microbial pathogens and proceeds via (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), a potent activ...

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Bibliographic Details
Published in:FEBS letters 2004-03, Vol.561 (1-3), p.99-104
Main Authors: Begley, Maire, Gahan, Cormac G M, Kollas, Ann-Kristin, Hintz, Martin, Hill, Colin, Jomaa, Hassan, Eberl, Matthias
Format: Article
Language:English
Subjects:
Listeria monocytogenes
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Summary:Isoprenoids are synthesised either through the classical, mevalonate pathway, or the alternative, non-mevalonate, 2-C-methyl-erythritol 4-phosphate (MEP) pathway. The latter is found in many microbial pathogens and proceeds via (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), a potent activator of human V gamma 9/V delta 2 T cells. Listeria monocytogenes is the only pathogenic bacterium known to contain both pathways concurrently. Strategic gene knockouts demonstrate that either pathway is functional but dispensable for viability. Yet, disrupting the mevalonate pathway results in a complementary upregulation of the MEP pathway. V gamma 9/V delta 2 T cell bioactivity is increased in Delta lytB mutants where HMB-PP accumulation is expected, and lost in Delta gcpE mutants which fail to produce HMB-PP.
ISSN:0014-5793
DOI:10.1016/S0014-5793(04)00131-0