ADAPTIVE ACID TOLERANCE OF STREPTOCOCCUS SOBRINUS

描述(申请人提供)：两种变形链球菌，变形链球菌和远缘链球菌，被认为是人类龋齿的主要病原体。虽然这两个物种都有很高的致龋性，但大多数研究都是在变形链球菌身上进行的；主要是因为在发达国家，变形链球菌与龋齿有很强的联系，但也因为与远缘链球菌相比，变形链球菌的基因操作相对容易。众所周知，变形链球菌比许多其他口腔细菌具有更强的耐酸性，并能够建立适应性耐酸反应(ATR)(Belli和Marquis，1991；Hamilton和Buckley，1991)。以前，远缘链霉菌虽然天生耐酸，但被认为缺乏安装ATR的能力(Svensater等人，1997年)。最近，我们实验室对远缘链霉菌对环境酸化的反应进行了更详细的分析(Nascimento等人，2004年)。我们的结果表明，远缘链霉菌实际上能够在酸性pH培养过程中产生旺盛的ATR。有趣的是，我们的数据表明，远缘链霉菌和变形链球菌在酸适应的分子机制上存在着关键的差异。在更耐人寻味的发现中，远缘链球菌在酸性条件下的F-ATPase的表达并没有像在许多其他生物中那样在酸性条件下被增强，而葡萄糖专一性的磷酸烯醇式丙酮酸糖：磷酸转移酶系统(PTS)的表达在低pH条件下生长的变形链霉菌中受到抑制，在pH 5.0的远缘链霉菌细胞中的表达是在pH 7.0的生长细胞中的两倍(Nascimento等人，2004年)。本申请的目的是通过以下具体目标扩展我们对远缘链霉菌ATR的研究：(I)远缘链霉菌耐酸反应的鉴定和特性；(Ii)缺乏PTS葡萄糖特异酶II(EIIGIc)的远缘链霉菌菌株的耐酸特性分析。

DESCRIPTION (provided by applicant): Two species of mutans streptococci, Streptococcus mutans and Streptococcus sobrinus, are considered the primary etiological agents of human dental caries. Although both species are highly cariogenic, the majority of studies have been carried out with S. mutans; primarily because of the strong association of S. mutans with caries in developed nations, but also because of the relative ease of genetic manipulation of S. mutans compared to S. sobrinus. It is well known that S. mutans is inherently more acid resistant than many other oral bacteria and is able to mount an adaptive acid tolerance response (ATR) (Belli and Marquis, 1991; Hamilton and Buckley, 1991). Previously, S. sobrinus, although intrinsically acid tolerant, was considered to lack the capacity to mount an ATR (Svensater et al., 1997). Recently, our laboratory conducted a more detailed analysis of the responses of S. sobrinus to environmental acidification (Nascimento et al., 2004). Our results indicated that S. sobrinus was in fact capable of developing a vigorous ATR during cultivation at acidic pH. Interestingly, our data indicated that there are critical differences in the molecular mechanisms of acid adaptation by S. sobrinus and S. mutans. Among the more intriguing findings, expression of the F-ATPase of S. sobrinus was not enhanced by growth in acidic conditions, as it is in many other organisms, and expression of the glucose-specific phosphoenolpyruvate sugar: phosphotransferase system (PTS), which in S. mutans is repressed during growth at low pH, was two-fold higher in S. sobrinus cells grown at pH 5.0 compared to pH 7.0-grown cells (Nascimento et al., 2004). The goal of this application is to extend our investigations on the S. sobrinus ATR by pursuing the following specific aims: (i) Identification and characterization of acid tolerance responses of S. sobrinus, and (ii) analysis of the acid tolerance properties of a S. sobrinus strain lacking the glucose-specific enzyme II (EIIGIc) of the PTS.