H2S PRODUCTION AND VIRULENCE OF TREPONEMA DENTICOLA

描述(改编自《调查者摘要》)：一个特征 牙周炎的特征是存在各种挥发性硫 在破坏性疾病发生的地方产生的化合物。硫化氢(H2S)是一种 这个家庭的主要成员，这是与口臭有关的主要因素 对牙周炎，更重要的是，可以影响宿主分子和细胞。 以前的研究已经确定了有限的口腔微生物谱系。 可以在含有大量硫化氢的微环境中产生和生存； 然而，参与硫化氢产生的代谢酶很少。 明白了。大量文献已经确认齿纹夜蛾是一种 很少有口腔细菌能够在高水平的硫化氢中产生和生长。 首席调查员之前已经分离并鉴定了一种酶， 胱氨酸菌素。这种酶是齿假单胞菌所特有的，有底物。 L的专一性-半胱氨酸，产丙酮酸、氨气，重要的是硫化氢。这 该提议发展了一个普遍的假设，即硫化氢是 牙周病区局部微环境中的宿主反应 此外，形成硫化氢的酶应该被认为是毒力 齿状毛滴虫的决定因素。三个特定的目标是使用 生物化学、分子遗传学和细胞生物学研究来解决这个问题 假设：具体目标1：构建改变的等基因突变体 半胱氨酸酶导向的硫化氢生产能力.具体目标2：生物化学 描述谷胱甘肽产生硫化氢的酶途径(S)； 具体目标3：确定由以下因素造成的硫化氢环境的影响 登革热对宿主炎症/免疫功能的影响。齿纹夜蛾一直是 被鉴定为特定微生物群体中的重要成员 被认为是破坏的发展和进展的病因 牙周组织。该提案旨在提供关键信息 与T.denticola产生H_2S有关，并首次 勾勒出硫化氢的潜在功能，这可能有害地影响 动态平衡，由牙周组织中的分子和细胞维持。这个 预计结果也将提供动力，以进一步实现 促进硫化氢产生的酶途径作为一种创新干预措施 策略。

DESCRIPTION (Adapted from the Investigator's Abstract): A characteristic feature of periodontitis is the existence of a variety of volatile sulfur compounds produced at sites of destructive disease. Hydrogen sulfide (H2S) is a major component of this family, which is a primary factor in halitosis related to periodontitis, and importantly, can affect host molecules and cells. Previous studies have identified a limited repertoire of oral microorganisms that can produce and survive in microenvironments with large amounts of H2S; however, the metabolic enzymes involved in the production of H2S are poorly understood. Substantial literature has identified T. denticola as one of the few oral bacteria with the capacity to produce and grow in high levels of H2S. The Principal Investigator has previously isolated and characterized an enzyme, cystalysin. This enzyme is unique to T. denticola and has a substrate specificity for L-cysteine, yielding pyruvate, NH3, and importantly, H2S. This proposal develops the general hypothesis that H2S is a significant effector of host responses in the local microenvironment of the periodontal disease site and, furthermore, that H2S-forming enzymes should be considered virulence determinants for T. denticola. Three specific aims are developed using biochemical, molecular genetic, and cell biologic studies to address this hypothesis: Specific Aim 1: To construct isogenic mutants altered in cystalysin-directed H2S producing capacity; Specific Aim 2: To biochemically characterize the enzyme pathway(s) involved in H2S production from glutathione; and, Specific Aim 3: To determine the effects of an H2S environment created by T. denticola on host inflammatory/immune functions. T. denticola has been identified as an important member of a specific consortia of microorganisms considered as etiologic in the development and progression of destruction of the periodontium. This proposal is designed to provide critical information related to the production of H2S by T. denticola, and for the first time to delineate the potential functions of H2S, which could deleteriously affect the homeostasis, maintained by molecules and cells in the periodontium. The outcomes would also be expected to provide an impetus to further target the enzymatic pathways contributing to H2S production as an innovative intervention strategy.