ACID/BASE PHYSIOLOGY OF ORAL STREPTOCOCCI

这个应用程序是为了支持一个专注于酸碱的项目 菌斑细菌的生理学，特别是变形链球菌，但 还有干酪乳杆菌和精氨酸脱亚胺酶阳性链球菌。 这项拟议的工作源于之前对耐酸性的研究 特别注意质子转运的F-ATPase。A基本的 假设斑块中耐酸性更强的细菌也是 致龋性更强。要想致龋性，细菌必须能够定居。 菌斑，成为菌群的重要组成部分，并产生酸。 然而，由于对牙齿的挑战与 斑块的酸化程度，那些可以降低 菌斑的酸碱值低至0.4是特别有害的。结果是 我们先前的工作表明F-ATPase对酸有两种适应性 宽容。耐受性越强的生物体， 单位菌体重量，酶的最适pH值较低。 计划将这些结果推广到其他生物体，特别是 耐酸、非突变、菌斑链球菌。拟议的工作将 现在考虑酶的质子转移效率 耦合比，即每个ATP传输多少质子 水解，意味着抑制酶并影响酶的效率 偶联，以及乳酸在质子中运输的可能参与 洋流。变形链球菌GS-5分离的膜泡 将被广泛用于拟议的工作，以及细菌的生长 在各种条件下的生物膜中。此外，分离的基因 因为变形链球菌的ATP操纵子将被用于研究调节 F-ATPase的合成。 在菌斑的整个酸碱循环中，氨的产生 精氨酸脱亚胺酶阳性细菌被认为对 保护耐酸性较差的细菌免受酸损害 降低致龋性。建议进行研究，以规管 血链球菌和链球菌氧化还原电位对精氨酸脱亚胺系统(ADS)的影响 Rattus，在ADS阴性突变体上，在生物膜中生长的细胞上 精氨酸肽的跨膜转运。 我们以前的工作和其他人的工作结果表明是重叠的 菌斑链球菌对酸保护的适应性 例如，由以下物质造成的损害和抗氧化损害 过氧化氢。我们建议更详细地定义ACID的性质 损害，特别是对糖酵解系统的损害，以及 酸损伤和氧化损伤。一个主要目标将是发展 意味着，例如，使用氧化损伤增强剂来减少酸 耐受性和致龋性。

This application is for support of a project focused on the acid-base physiology of plaque bacteria, especially the mutans streptococci, but also Lactobacillus casei and arginine-deiminase positive streptococci. The proposed work arises from previous studies the acid tolerance with particular attention on proton-translocating F-ATPases. A basic hypothesis is that the more acid-tolerant bacteria in plaque are also the more cariogenic. To be cariogenic, a bacterium must be able to colonize plaque, become a significant part of the flora, and produce acid. However, since the challenge to the tooth is exponentially related to the extent of acidification of plaque, those organisms which can lower the plaque pH to values as low as .4 are particularly damaging. The results of our prior work indicated two adaptations in F-ATPases for acid tolerance. More tolerant organisms have higher F-ATPase activities per unit of cell weight, and the enzymes have lower pH optima for activity. Plans are to extend these results with other organisms, especially the acid-tolerant, non-mutants, plaque streptococci. The proposed work will now consider proton-translocating efficiencies of the enzymes in terms of coupling ratios i.e., how many protons are transported per ATP hydrolyzed, means to inhibit the enzyme and to affect the efficiency of coupling, and the possible involvement of lactate transport in proton currents. Membrane vesicles isolated from Streptococcus mutans GS-5 will be used extensively for the proposed work, as will bacteria grown in biofilms under a variety of conditions. In addition, isolated genes for the atp operon of S. mutans will be used for studies of regulation of F-ATPase synthesis. In the overall acid-base cycles of plaque, ammonia production by arginine-deiminase-positive bacteria is considered important for protecting less acid-tolerant bacteria against acid damage and for reducing cariogenicity. Studies are proposed on regulation of the arginine deiminase system (ADS) by redox potential in S. sanguis and S. rattus, on ADS-negative mutants, on cells grown in biofilms and on transmembrane transport of arginine peptides. The results of our previous work and that of others has indicated overlap in the adaptations of plaque streptococci for protection against acid damage and against oxidative damage caused, for example, by hydroperoxides. We proposed to define in more detail the nature of acid damage, especially to the glycolytic system, and the relationship between acid damage and oxidative damage. A major objective will be to develop means, for example, with enhancers of oxidative damage, to reduce acid tolerance and cariogenicity.