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

FEBS Letters

Begley, Máire²  Eberl, Matthias¹  Hill, Colin²  Kollas, Ann-Kristin¹  Gahan, Cormac G.M.²  Hintz, Martin¹  Jomaa, Hassan¹ 

[1] Biochemisches Institut, Infektiologie, Justus-Liebig-Universität Giessen, Friedrichstr. 24, 35392 Giessen, Germany;Department of Microbiology and Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland

关键词: HMG-CoA;    gcpE;    lytB;    Hydroxymethylbutenyl pyrophosphate;    Isopentenyl pyrophosphate;    Listeriosis;    HMB-PP;    (E)-4-hydroxy-3-methyl-but-2-enyl-pyrophosphate;    GcpE;    (E)-4-hydroxy-3-methyl-but-2-enyl-pyrophosphate synthase;    LytB;    (E)-4-hydroxy-3-methyl-but-2-enyl-pyrophosphate reductase;    HMG-CoA;    3-hydroxy-3-methylglutaryl-coenzyme A;    IPP;    isopentenyl pyrophosphate;    LMW;    low molecular weight;    MEP;    2-C-methyl-D-erythritol 4-phosphate;   

DOI  :  10.1016/S0014-5793(04)00131-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 Vγ9/Vδ2 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. Vγ9/Vδ2 T cell bioactivity is increased in ΔlytB mutants where HMB-PP accumulation is expected, and lost in ΔgcpE mutants which fail to produce HMB-PP.

【 授权许可】

Unknown