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，允许更多地购买糖果，龋齿的增长也在增长。即使在美国，也有大约80%的龋齿在20%的人口中存在问题，并且该疾病变得终身，因为老年美国人保留他们的牙齿，同时减少唾液流成为他们服用的药物。此外，本港亦有迹象显示，儿童患龋的情况正逐渐增加，虽然速度缓慢。总体而言，龋齿似乎没有得到控制，即使在工业化国家。龋齿的最佳控制策略包括降低病原体的毒力。对于诸如变形链球菌的生物体，控制可以依赖于抑制口腔附着，主要是牙菌斑，或降低酸耐受性。由于龋齿主要发生在低pH值，毒力与耐酸性密切相关，耐酸性似乎主要由F（H+）-ATP酶，特别是由每个细胞的酶量和特定细菌的酶的pH活性谱来设定。本申请的重点是耐酸性和F-ATP酶。它建议继续进行中的研究，但也解决了龋齿的多生物体病因学，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.进一步研究口腔细菌的F-ATP酶，旨在确定高耐受性和低耐受性微生物的酶之间的耐酸性差异的分子基础，并评估微生物的F-ATP酶活性的生理控制因素，包括ATP供应和与膜脂质的关联。膜脂肪酸对跨膜转运系统的调节也将被研究; 2. 通过在酸化培养基中生长从菌斑中筛选的口腔链球菌耐酸菌株的酸碱生理学研究。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，发展酸适应性反应的能力，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.