COORDINATION OF S MUTANS SUCROSE METABOLISM

这是修改后的R29应用程序。变形链球菌致龋性是 与其蔗糖代谢相关的多个途径，其中 一些人制造用于定居和能量储存的糖聚合物，而 另一些则会产生导致牙齿腐烂的酸。最近的研究表明 有几种途径，FTF、gftBC和SCRA是由蔗糖诱导的，而 SCRA被果糖抑制，果糖是GTF活性的产物。男男性接触者 操纵子在细胞内由果糖、G-1-P和G-6-P诱导，它们是 不同途径的蔗糖代谢产物。因此，可以假设S。 变形菌表现出几个蔗糖途径的协同表达。这个 协调表达可能由蔗糖代谢物介导，如 果糖或G-1-P，可由一条途径和交叉- 监管另一个人。当糖不可用时，多糖会降解 对糖饥饿的反应可能诱导通路释放游离糖 糖，这反过来又可能交叉调节其他途径。 到目前为止，已经鉴定了13条变形链球菌的蔗糖代谢途径。 其中，对九条主要途径进行了遗传学研究： GTFB、gtfc、gtfD、ftf；DEXA、FRU、scrAB、MSM和GLG；其余四家 是海藻糖、葡萄糖和果糖的PTS途径和糖原 降解途径。因为九大物种的基因和突变体 路径是可用的，我们可以立即开始检验这一假设。 我们建议：(1)确定其他途径对MSM的交叉调节， DEXA或FRUA，可通过显色化学物质直接监测， 使用同基因的突变体。(2)确定其他途径的交叉调节 关于FTF、gtfBC、SCRA和GLG，它们没有现成的可分析 表型，使用其中一条途径与报告基因融合的菌株 基因，而另一个是灭活的。(3)评估交叉监管 同时在多条路径之间。(4)识别诱导 多糖对糖饥饿反应的降解途径。这个 这些结果将有助于我们了解变形链球菌的基因调控。 蔗糖代谢，这对变形链球菌的毒力是至关重要的。

This is a revised R29 application. Streptococcus mutans cariogenicity is associated with its sucrose metabolism via multiple pathways, among which some make sugar polymers for colonization and energy storage, while others produce acid that causes tooth decay. Recent studies have shown that several pathways, ftf; gftBC and scrA, are induced by sucrose, while scrA is repressed by fructose, a product of the Gtf activity. The msm operon is induced intracellularly by fructose, G-1-P and G-6-P, which are sucrose metabolites of various pathways. It is thus hypothesized that S. mutans shows coordinated expression of several sucrose pathways. The coordinated expression may be mediated by sucrose metabolites, such as fructose or G-1 -P, which may be generated from one pathway and cross- regulate another. When sugar is unavailable, polysaccharide-degradation pathways may be induced in response to sugar starvation to release free sugars, which in turn may cross-regulate other pathways. To date, 13 sucrose metabolic pathways of S. mutans have been identified. Among them, nine major pathways have been genetically studied: these are gtfB, gtfC, gtfD, ftf; dexA, fru, scrAB, msm and glg; the remaining four are the trehalose, glucose and fructose PTS pathways and the glycogen degradation pathway. Since the genes and mutants of the nine major pathways are available, we can begin testing this hypothesis immediately. We propose to: (1) Identify cross-regulation of other pathways on msm, dexA or fruA, which can be monitored directly by chromogenic chemicals, using isogeneic mutants. (2) Identify cross-regulation of other pathways on ftf, gtfBC, scrA and glg, which do not have a readily assayable phenotype, using strains in which one pathway is fused with a reporter gene and the other is inactivated. (3) Evaluate cross-regulation simultaneously among multiple pathways. (4) Identify induction of polysaccharidedegradation pathways in response to sugar starvation. The results will help us understand the genetic regulation of S. mutans sucrose metabolism, which is critical for S. mutans virulence.