Acid/Base Physiology of Oral Streptococci

龋齿仍然是当今世界的一种主要疾病，其增长是由于世界人口的增加和发展中国家可支配收入的增加，使其能够购买更多的糖果。即使在美国，20%的人口中有80%的人患有龋齿，而且这种疾病已经成为终身疾病，因为美国老年人在保留牙齿的同时，由于他们服用的药物，唾液流减少了。此外，当地有迹象表明，儿童龋齿正在增加，尽管速度缓慢。总体而言，即使在工业化国家，龋齿似乎也未得到控制。龋齿的最佳控制策略包括降低病原体的毒力。对于变异链球菌等生物，控制可依赖于抑制口腔附着，主要是对菌斑的附着，或降低酸耐受性。由于龋齿主要发生在低pH值，毒力与酸耐受性密切相关，这似乎主要由F(H+)- atp酶决定，特别是由每个细胞的酶数量和特定细菌的酶的pH活性谱决定。该应用侧重于耐酸和f - atp酶。它建议继续进行正在进行的研究，但也提出了龋齿的多生物病因学，膜酶的脂肪酸调节和F- atp酶活性的底物限制的新观点。具体目标是：1。对口腔细菌F-ATP酶的进一步研究，旨在确定高耐酸性和低耐酸性生物的酶之间酸耐受性差异的分子基础，并评估生物F-ATP酶活性的生理控制因素，包括ATP供应和与膜脂的关系。膜脂肪酸对跨膜运输系统的调节也将被研究；2. 从牙菌斑中选择的耐酸口腔链球菌菌株在酸化培养基中生长的酸碱生理学研究。这项工作将包括研究生物体的f - atp酶，与变形链球菌相比，细胞对生物体的缓冲能力，对氟化物和其他弱酸的反应，产生酸适应反应的能力，以及其他可能允许在低pH值下产生糖酵解酸的因素。

Dental caries continue to be a major disease in the world today with growth due to increasing world population and greater availability of disposable income in developing countries allowing for greater purchases of sweets. Even in the United States, there is a problem of some 80% of the caries in 20% of the population and the disease become lifelong now that older Americans are retaining their teeth while at the same time having reduced salivary flow become of the medicines they take. Moreover, there are indications locally that caries in children is increasing, albeit slowly. Overall, caries appears not to be under control, even in industrialized countries. The best control strategies for caries involve reducing the virulence of the pathogens. For organisms such as mutans streptococci, control can depend on inhibition of oral attachment, mainly to plaque, or reductions in acid tolerance. Since caries occurs mainly at low pH values, virulence is closely related to acid tolerance, which appears to be set mainly by F(H+)-ATPases, specifically by amounts of the enzyme per cell and pH-activity profiles of the enzymes of particular bacteria. This application is focused on acid tolerance and F-ATPases. It proposes continuation of ongoing research but also addresses new views of the multi-organism etiology of caries, of fatty- acid modulation of membrane enzymes and of substrate limitation of F- ATPase activities. The specific aims are: 1. Further studies of the F- ATPases of oral bacteria with orientation to defining the molecular bases for differences in acid tolerance among the enzymes of organisms with high and low tolerance and to evaluation of physiological controlling factors for the F-ATPase activities of the organisms, including ATP supply and associations with membrane lipids. Modulation of transmembrane transport systems by membrane fatty acids will be investigated also; 2. Studies of the acid-base physiology of acid-tolerant strains of oral streptococci selected from plaque through growth in acidified media. The work will include studies of the F-ATPase of the organisms, buffer capacities of cells to the organisms compared with mutans streptococci, responses to fluoride and other weak acids, capacities to develop acid-adaptive response, and other factors that may allow for glycolytic acid production at low pH values.