ADAPTATION TO ENVIRONMENTAL STRESSES AND DENTAL CARIES

在菌斑中，细菌通常会受到酸应激， 宿主摄取可发酵的碳水化合物。致龋生物 例如变异链球菌可以在生理上适应酸应激。 这种适应可以在不到一代细胞的时间内发生， 质子转运F-ATP酶以及其他酶的活性增加， 目前应对酸化的机制不明确。因此，在本发明中， 致龋细菌不仅具有高的基础或组成水平， 抗酸胁迫，但可以增加他们的抵抗力， 诱导适应机制类似类型的酸适应发生在 肠道细菌，并用于增强抵抗杀死在 吞噬溶酶体的酸化环境。这其中的主要焦点 应用将是对生理和分子表征的 变形链球菌对酸胁迫的适应性反应， 与对其他压力的反应重叠，例如导致斑块。 变形链球菌的酸适应细胞能在pH值下进行糖酵解 值低于未适应细胞的最小值， 牙菌斑将转化为增强的脱矿潜力，即。 例如，增强的致龋性。除变形链球菌以外的菌斑细菌 可以适应酸性胁迫，这种适应，包括去抑制， 精氨酸脱亚胺酶系统在生物体，如链球菌 sanguis可能在整个斑块生态学中具有重要意义。 然而，本申请中的定向主要针对变异体 链球菌。 该项目的三个具体目标是：l）制定一个更完整的 变异体对酸胁迫适应的生理学定义 链球菌和密切相关的细菌，2）识别和表征 酸调节蛋白和变异链球菌基因，和3）携带 主要从分子遗传学角度分析其调控和功能 变形链球菌应激反应蛋白 参与该项目的三个实验室的协调努力 将通过项目内的互动来补充，特别是在 重金属和唾液肽对 致龋性这项工作的一个长期目标是设计方法， 扰乱反应，从而降低牙斑致龋性。

In plaque, bacteria are routinely subjected to acid stresses following ingestion of fermentable carbohydrates by the host. Cariogenic organisms such as the mutans streptococci can adapt physiologically to acid stress. This adaptation can occur in less than a cell generation and involves increased activities of proton-translocating F-ATPases as well as other, currently ill-defined mechanisms of coping with acidification. Thus, cariogenic bacteria not only have a high basal or constitutive level of resistance to acid stress but can increase their resistance through inducible adaptive mechanisms. Similar types of acid adaptation occur in enteric bacteria and serve to enhance resistance to killing in the acidified environment of the phagolysosome. The major focus of this application will be on physiologic and molecular characterization of the adaptive responses of mutans streptococci to acid stress, which are likely to overlap with responses to other stresses such as to lead in plaque. Acid-adapted cells of mutans streptococci can carry out glycolysis at pH values lower than the minimum for unadapted cells, and this ability in plaque would translate into enhanced potential for demineralization, i. e., enhanced cariogenicity. Plaque bacteria other than mutans streptococci can adapt to acid stress, and this adaptation, which includes derepression of the arginine deiminase system in organisms such as Streptococcus sanguis, is likely to be of major importance in overall plaque ecology. However, the orientation in this application is primarily to mutans streptococci. The three specific aims of the project are: l) to develop a more complete physiological definition of adaptation to acid stress in mutans streptococci and closely related bacteria, 2) to identify and characterize acid-regulated proteins and genes of mutans streptococci, and 3) to carry out molecular genetic analysis of the regulation and function of major stress response proteins in mutans streptococci. The coordinated efforts of the three laboratories involved in this project will be supplemented by interactions within the program, especially in relation to effects of heavy metals and salivary peptides on cariogenicity. A long term objective of the work is to design means to upset the responses and thereby to lower plaque cariogenicity.