ADAPTIVE ACID TOLERANCE OF STREPTOCOCCUS SOBRINUS

描述（由申请人提供）：两种变形链球菌，变形链球菌和红链球菌，被认为是人类龋齿的主要病原。虽然这两个物种都是高度致龋的，但大多数研究都是用变形链球菌进行的；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sobrinus相比，变形链球菌的基因操作相对容易。众所周知，变形链球菌天生比许多其他口腔细菌更耐酸，并能够产生适应性耐酸反应（ATR） （Belli and Marquis, 1991; Hamilton and Buckley, 1991）。以前，尽管S. sobrinus本身耐酸，但被认为缺乏装载ATR的能力（Svensater et al., 1997）。最近，我们的实验室对S. sobrinus对环境酸化的反应进行了更详细的分析（Nascimento et al., 2004）。我们的研究结果表明，sobrinus实际上能够在酸性ph培养过程中产生强烈的ATR。有趣的是，我们的数据表明，sobrinus和S. mutans在酸适应的分子机制上存在关键差异。在更有趣的发现中，S. sobrinus的f - atp酶的表达并没有因为在酸性条件下生长而增强，就像在许多其他生物中一样，并且葡萄糖特异性磷酸烯醇丙酮酸糖：磷酸转移酶系统（PTS）的表达，在S. mutans中在低pH下生长时被抑制，在pH 5.0下生长的S. sobrinus细胞中比pH 7.0生长的细胞高出两倍（Nascimento等人，2004）。本申请的目标是通过追求以下具体目标来扩展我们对S. sobrinus ATR的研究：(i)鉴定和表征S. sobrinus的耐酸反应，以及（ii）分析S. sobrinus菌株缺乏PTS的葡萄糖特异性酶ii （EIIGIc）的耐酸特性。

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.