Acid/Base Physiology of Oral Streptococci

龋齿仍然是当今世界的一种主要疾病，由于世界人口的增加和发展中国家可支配收入的增加，使得人们能够更多地购买糖果，所以龋齿仍在增长。即使在美国，20%的人口中也有大约80%的龋齿问题，这种疾病是终生的，因为美国老年人保留了他们的牙齿，同时减少了唾液流量，这是他们服用的药物的结果。此外，当地有迹象表明，儿童的龋齿正在增加，尽管速度很慢。总体而言，龋病似乎没有得到控制，即使在工业化国家也是如此。控制龋齿的最佳策略包括降低病原体的毒力。对于像变形链球菌这样的生物，控制可能取决于抑制口腔附着，主要是对菌斑的附着，或者降低耐酸性。由于龋病主要发生在低pH值，毒力与耐酸性密切相关，这似乎主要由F(H+)-ATPase决定，特别是由每个细胞的酶的数量和特定细菌的酶的pH活性曲线决定的。这方面的应用主要集中在耐酸性和F-ATPase方面。它建议继续正在进行的研究，但也提出了关于龋病的多生物病因、膜酶的脂肪酸调节和F-ATPase活性的底物限制的新观点。1.口腔细菌F-ATPase的进一步研究，旨在明确高耐受性生物和低耐受性生物酶耐酸性差异的分子基础，并评价生物F-ATPase活性的生理控制因素，包括ATP供应和与膜脂的结合。此外，还将研究膜脂肪酸对跨膜转运系统的调节作用；2.从菌斑中筛选出的耐酸型口腔链球菌在酸化介质中生长的酸碱生理研究。这项工作将包括研究生物体的F-ATPase，细胞与变形链球菌相比对生物体的缓冲能力，对氟化物和其他弱酸的反应，形成酸适应反应的能力，以及可能允许在低pH值下产生糖酵解酸的其他因素。

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.