The interplay between classical and alternative isoprenoid biosynthesis controls γδ T cell bioactivity of Listeria monocytogenes
The interplay between classical and alternative isoprenoid biosynthesis controls γδ T cell bioactivity of Listeria monocytogenes
复制标题
DOI：
10.1016/s0014-5793(04)00131-0
复制
发表时间：
2004-03-12
期刊：
影响因子：
3.5
通讯作者：
Eberl, M
中科院分区：
文献类型：
--
作者：
Begley, M;Gahan, CGM;Eberl, M
类异戊二烯通过经典的甲羟戊酸途径或替代的非甲羟戊酸的2-C-甲基-D-C4-磷酸（MEP）途径合成。后者存在于许多微生物病原体中，并通过（E）-4羟基-3-甲基-丁-2-烯基焦磷酸（HMB-PP）进行，HMB-PP是人V γ 9/Vdelta 2 T细胞的有效激活剂。单核细胞增生李斯特菌是唯一已知同时含有这两种途径的致病细菌。战略基因敲除表明，任何途径是功能性的，但缺乏活力。然而，破坏甲羟戊酸途径导致MEP途径的互补上调。Vgamma 9/Vdelta 2 T细胞生物活性在预期HMB-PP积累的DeltalytB突变体中增加，并且在不能产生HMB-PP的DeltagcpE突变体中丧失。(C)2004年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
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)-4hydroxy-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. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.