S MUTANTS GLG GENE EXPRESSION

描述(摘自调查者摘要)：变形链球菌， 是人类龋齿的主要病原体，感染的人数超过 世界上95%的人口，经常在 生命的第一年。在对S的贡献中突出的属性中。 变种致龋病是外源性膳食代谢的结果 碳水化合物；这会导致口腔中乳酸的产生 空洞导致牙釉质脱矿和牙周炎的发生 牙齿腐烂。外源碳水化合物只是S的一个来源。 然而，变种人的酸生产。另外，变形链球菌也可以产酸。 通过代谢细胞内多糖(IPS)，类糖原储存 聚合物。对变形链球菌的IPS及其机制知之甚少(S) 调节它们在斑块环境中的表达。因此，一项调查 将扩展我们对导致酸化的事件的了解 在口腔中产生，因此提供了新的治疗策略 防止龋齿。调查人员鉴定并克隆了 糖原(GLG)基因座参与变形链球菌IPS的积累和 证明了变形链球菌IPS是对 成龋性过程。具体地说，具有IPS缺陷的突变体携带 变形链球菌GLG基因座缺失的致龋性显著低于 它的野生型前体在无菌大鼠中，而一个转座子突变体 积累的IPS明显超过野生型水平 在这个动物模型中有高龋齿。这项研究的主要目标 建议阐明变形链球菌基因座的结构组织 并探讨了变形链球菌IPS积累的机制(S)。 在斑块环境中进行调节。具体目标包括1) 变形链球菌GLG基因座的连续核苷酸序列分析 环境中变形链球菌GLG基因表达特性的研究 哪些近似于口腔，3)调控的识别 控制变形链球菌GLG基因表达的因素，以及4) 变形链球菌GLG操纵子之间可能的交叉调节研究 和其他影响口腔中蔗糖代谢的遗传基因座 病原体。事实上，这些研究将进一步加深我们对 在斑块环境中导致酸产生的事件 阐明运行以优化致龋性的调控网络 变形链球菌的潜力。

DESCRIPTION (Adapted from investigator's Abstract): Streptococcus mutans, the principal etiologic agent of dental caries in humans, infects more than 95% of the population worldwide, often colonizing the oral cavity during the first year of life. Prominent among the attributes which contribute to S. mutans-induced caries formation is the metabolism of exogenous dietary carbohydrates; this results in the production of lactic acid in the oral cavity which leads to the demineralization of tooth enamel and the onset of dental decay. Exogenous carbohydrates represent only one source of S. mutans acid production, however. Alternatively, S. mutans can produce acid by metabolizing intracellular polysaccharides (IPS), glycogen-like storage polymers. Very little is known of S. mutans IPS and the mechanism(s) which regulate their expression in the plaque environment. Thus, an investigation of S. mutans IPS will extend our knowledge of the events which lead to acid production in the oral cavity and so provide novel treatment strategies for the prevention of tooth decay. The investigator identified and cloned the glycogen (glg) locus which is involved in S. mutans IPS accumulation and demonstrated that S. mutans IPS are significant contributors to the caries-forming process. Specifically, an IPS-deficient mutant which bears a deletion at the S. mutans glg locus is significantly less cariogenic than its wild-type progenitor in germfree rats, while a transposon mutant which accumulates IPS in excess of wild-type levels is significantly hypercariogenic in this animal model. The major goals of this research proposal are to elucidate the structural organization of the S. mutans locus and to investigate the mechanism(s) by which S. mutans IPS accumulation is regulated in the plaque environment. The specific aims include 1) the continued nucleotide sequence analysis of the S. mutans glg locus, 2) the characterization of glg gene expression in S. mutans grown in environments which approximate the oral cavity, 3) the identification of regulatory elements which govern S. mutans glg gene expression, and 4) the investigation of putative cross-regulation between the S. mutans glg operon and other genetic loci which contribute to sucrose metabolism in this oral pathogen. Indeed, these studies will further our understanding of the events which lead to acid production in the plaque environment by elucidating the regulatory network which operates to optimize the cariogenic potential of S. mutans.