OXIDATIVE STRESS IN ORAL STEPTOCOCCI

氧代谢和代谢产生的活性氧（ROS）引起的氧化损伤是影响斑块细菌活性的关键过程。生物体已经发展出多种机制来保护自己免受氧化损伤，包括超氧化物歧化酶、过氧化物酶、巯基还原酶和DNA修复酶。龈上菌斑的氧主要来源于口腔空气，龈下菌斑的氧主要来源于沟沟液。由于菌斑是一层很薄的生物膜，O2很容易进入被代谢的膜，并且通常发现菌斑的残余O2水平约为空气饱和水的10%。然而，重要的氧是代谢部分，这是ROS的来源。此外，许多口腔保健品含有过氧化氢，过氧化氢可通过芬顿反应自由基化，造成氧化损伤。这项应用的目的是对菌斑细菌（主要是口腔链球菌）的氧化损伤有一个更清晰的认识，并通过基因突变确定主要的保护机制。该项目的一部分有一个非常实际的目标，即设计更好的方法来控制口腔传染病，重点是龋齿和使用过氧化物。具体目标是：1。确定nadh连接的氧化酶、过氧化物酶和谷胱甘肽还原酶在保护口服链球菌抵抗过氧化氢和其他氧化损伤剂中的作用，2。2 .明确超氧化物和超氧化物歧化酶在氧化损伤和抗损伤保护中的作用。阐明过渡金属阳离子、螯合剂和氟化物在氧化损伤中的相互作用，包括与氧代谢酶和保护酶的相互作用。

Oxygen metabolism and resultant oxidative damage caused by metabolically generated reactive oxygen species (ROS) are key processes affecting the activities of plaque bacteria. The organisms have developed multiple mechanisms to protect themselves against oxidative damage, including superoxide dismutase, peroxidases, sulfhydryl reductases and DNA repair enzymes. The major source of O2 for supragingival plaque is air in the mouth, while that for subgingival plaque is crevicular fluid. Since plaque is a thin biofilm, O2 moves readily into the film to be metabolized, and plaque generally has been found to have residual O2 levels about 10% that of air-saturated water. However, the important O2 is the metabolized portion, which then is the source of ROS. In addition, many oral healthcare products contain hydrogen peroxide, which can be radicalized through Fenton reactions to cause oxidative damage. The objectives of this application are to develop a clearer picture of oxidative damage to plaque bacteria, primarily oral streptococci, and to identify through use of genetic mutants the major protective mechanisms. Part of the project has a very practical aim of devising better ways to control oral infectious diseases with an emphasis on caries and use of peroxides. The specific aims are: 1. Determine the roles played by NADH-linked oxidases, peroxidases and glutathione reductase in protection of oral streptococci against hydrogen peroxide and other oxidatively damaging agents, 2. Define the roles that superoxide and superoxide dismutase play in oxidative damage and protection against damage, 3. Elucidate the interactions of transition-metal cations, chelators and fluoride in oxidative damage, including interactions with oxygen- metabolizing and protective enzymes.