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首页> 外文期刊>Infection and immunity >Analysis of the Isoprenoid Biosynthesis Pathways in Listeria monocytogenes Reveals a Role for the Alternative 2-C-Methyl-d-Erythritol 4-Phosphate Pathway in Murine Infection
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Analysis of the Isoprenoid Biosynthesis Pathways in Listeria monocytogenes Reveals a Role for the Alternative 2-C-Methyl-d-Erythritol 4-Phosphate Pathway in Murine Infection

机译：单核细胞增生李斯特氏菌中类异戊二烯生物合成途径的分析揭示了小鼠感染中替代性2-C-甲基-d-赤藓糖醇4-磷酸途径的作用。

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Most bacteria synthesize isoprenoids through one of two essential pathways which provide the basic building block, isopentyl diphosphate (IPP): either the classical mevalonate pathway or the alternative non-mevalonate 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway. However, postgenomic analyses of the Listeria monocytogenes genome revealed that this pathogen possesses the genetic capacity to produce the complete set of enzymes involved in both pathways. The nonpathogenic species Listeria innocua naturally lacks the last two genes (gcpE and lytB) of the MEP pathway, and bioinformatic analyses strongly suggest that the genes have been lost through evolution. In the present study we show that heterologous expression of gcpE and lytB in L. innocua can functionally restore the MEP pathway in this organism and confer on it the ability to induce Vγ9Vδ2 T cells. We have previously confirmed that both pathways are functional in L. monocytogenes and can provide sufficient IPP for normal growth in laboratory media (M. Begley, C. G. Gahan, A. K. Kollas, M. Hintz, C. Hill, H. Jomaa, and M. Eberl, FEBS Lett. 561:99-104, 2004). Here we describe a targeted mutagenesis strategy to create a double pathway mutant in L. monocytogenes which cannot grow in the absence of exogenously provided mevalonate, confirming the requirement for at least one intact pathway for growth. In addition, murine studies revealed that mutants lacking the MEP pathway were impaired in virulence relative to the parent strain during intraperitoneal infection, while mutants lacking the classical mevalonate pathway were not impaired in virulence potential. In vivo bioluminescence imaging also confirmed in vivo expression of the gcpE gene (MEP pathway) during murine infection.
机译：大多数细菌通过提供基本构件的两个基本途径之一合成异戊二烯，即二戊基异戊基二磷酸（IPP）：经典的甲羟戊酸途径或另一种非甲羟戊酸2-C-甲基-d-赤藓糖醇4-磷酸（MEP）途径。然而，对单核细胞增生李斯特菌基因组的基因组分析表明，该病原体具有产生涉及这两种途径的完整酶的遗传能力。非致病性李斯特菌自然缺乏MEP途径的后两个基因（ gcpE 和 lytB ），生物信息学分析强烈提示该基因通过进化而迷失了。在本研究中，我们显示了 gcpE 和 lytB 在 L中的异源表达。无毒菌可以在该生物体中功能恢复MEP途径，并赋予其诱导Vγ9Vδ2T细胞的能力。我们先前已经证实，这两种途径在 L中均起作用。并能为实验室培养基的正常生长提供足够的IPP（M. Begley，CG Gahan，AK Kollas，M.Hintz，C.Hill，H.Jomaa和M.Eberl，FEBS Lett.561：99 -104，2004年。在这里，我们描述了一种有针对性的诱变策略，以在 L中创建双途径突变体。在缺乏外源性甲羟戊酸的情况下不能生长的单核细胞增生因子，这证实了至少需要一个完整的生长途径。此外，鼠类研究表明，在腹膜内感染过程中，缺少MEP途径的突变体相对于亲本菌株的毒力受损，而缺乏经典甲羟戊酸途径的突变体的毒力潜力没有受到损害。体内生物发光成像也证实了在小鼠感染期间 gcpE 基因（MEP途径）在体内的表达。

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