The interplay between classical and alternative isoprenoid biosynthesis controls gammadelta T cell bioactivity of Listeria monocytogenes.
Isoprenoids are synthesised either through the classical, mevalonate pathway, or the alternative, non-mevalonate, 2-C-methyl-D-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 Vgamma9/Vdelta2 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. Vgamma9/Vdelta2 T cell bioactivity is increased in DeltalytB mutants where HMB-PP accumulation is expected, and lost in DeltagcpE mutants which fail to produce HMB-PP.
Begley
Máire
M
Department of Microbiology and Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.
Gahan
Cormac G M
CG
Kollas
Ann-Kristin
AK
Hintz
Martin
M
Hill
Colin
C
Jomaa
Hassan
H
Eberl
Matthias
M
D011756:Diphosphates / Q000378:metabolism; D004896:Erythritol / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation; D008798:Mevalonic Acid / Q000378:metabolism; D009154:Mutation; D016692:Receptors, Antigen, T-Cell, gamma-delta; D013403:Sugar Phosphates / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000382:microbiology*; D013729:Terpenes / Q000378:metabolism*
C114232:2-C-methylerythritol 4-phosphate; C443995:4-hydroxy-3-methylbut-2-enyl pyrophosphate; D011756:Diphosphates; D016692:Receptors, Antigen, T-Cell, gamma-delta; D013403:Sugar Phosphates; D013729:Terpenes; D004896:Erythritol; D008798:Mevalonic Acid