S MUTANTS GLG GENE EXPRESSION

描述（改编自研究者摘要）：变形链球菌， 人类龋齿的主要病原体， 全世界95%的人口，经常在口腔中定居， 生命的第一年。 在有助于S的属性中突出。 致龋突变体的形成是外源性饮食的代谢 碳水化合物;这导致口腔中产生乳酸 导致牙釉质脱矿的空腔和 蛀牙 外源性碳水化合物仅代表S的一种来源。 然而，变异酸的产生。 或者，S.变形菌能产生酸 通过代谢细胞内多糖（IPS），糖原样储存 聚合物 很少有人知道S。变异的IPS和机制， 调节它们在斑块环境中的表达。 因此，一项调查 色葡萄变异的IPS将扩大我们的知识的事件，导致酸 因此提供了新的治疗策略， 防止蛀牙。 研究人员发现并克隆了 糖原（glg）基因座。变形杆菌IPS蓄积和 证明S.变异的IPS是重要的贡献者， 龋齿形成过程 具体地，具有一个突变体的IPS缺陷型突变体， 在S.变形菌GLG基因座的致龋性显著低于 其野生型祖细胞在无菌大鼠，而转座子突变体， IPS的积累超过野生型水平， 在这个动物模型中， 本研究的主要目标是 建议是阐明结构组织的S。变异基因座 并探讨S.变形杆菌IPS蓄积是 在菌斑环境中调节。 具体目标包括：（1） 继续对S.变形链球菌glg基因座，2） glg基因在S.环境中生长的变异体 3）确定调节性的 控制S的元素。变形链球菌glg基因表达，以及4） 研究S.变形链球菌glg操纵子 和其他遗传位点，有助于蔗糖代谢，在这个口腔 病原体 事实上，这些研究将进一步加深我们对 导致菌斑环境中酸产生的事件， 阐明了优化致龋的调节网络， 潜力S。变异人

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.