Oxygen and Streptococcus mutans Virulence

描述（由申请人提供）：我们已经确定变形链球菌关键毒力属性的基因表达，包括那些涉及生物膜形成、碳水化合物运输、酸生产、储存聚合物分解代谢和外多糖生产的基因，受到氧气暴露的显著影响。此外，我们已经揭示了复杂的控制电路，用于响应氧化还原的细胞表面重塑，其中一些我们已经证明是由双组分系统和自溶素集中调节的。本提案的目的是了解变形链球菌在氧气存在下生长的表型后果，并剖析我们观察到的变形链球菌在空气中培养时是完全不同的生物体的潜在分子基础。为了实现这些目标，我们制定了以下具体目标。目的1。厌氧与好氧培养细胞毒力相关表型特性的比较[j]。厌氧与好氧培养细胞表面和分泌组的比较通过实施这些目标的研究计划，将实现对S. mutans对空气和厌氧反应的全面了解。这些研究将直接导致更好地了解这种病原体在未成熟和成熟牙菌斑中的行为。这一研究路线已经发现，并将继续揭示可能作为破坏变形链球菌建立和持续的目标的新途径。建议的研究具有广泛的相关性，并将促进发展对抗龋齿和其他疾病的新疗法。

DESCRIPTION (provided by applicant): We have established that the expression of genes for critical virulence attributes of Streptococcus mutans, including those involved in biofilm formation, carbohydrate transport, acid production, catabolism of storage polymers, and exopolysaccharide production, is dramatically affected by exposure to oxygen. Moreover, we have disclosed complex control circuits for remodeling of the cell surface in response to redox, some of which we have shown to be centrally regulated by a two- component system and autolysin. The goals of this proposal are to understand the phenotypic consequences of growth of S. mutans in the presence of oxygen and to dissect the underlying molecular basis for our observations that S. mutans is a radically different organism when cultured in air. To achieve these goals, the following Specific Aims are established. Aim 1. Comparison of virulence-related phenotypic properties of cells cultured anaerobically or aerobically Aim 2. Comparison of the surface and secretome of cells cultured anaerobically or aerobically Aim 3. Analysis of cis- and trans-acting elements of O2-responsive genes By implementing the Research Plan for these aims, a comprehensive understanding of the responses of S. mutans to air and anaerobiosis will be realized. These studies will lead directly to a better understanding of the behavior of this pathogen in immature and mature dental plaque. This line of investigation has already discovered, and will continue to disclose, novel pathways that may serve as targets to disrupt the establishment and persistence of S. mutans. The proposed studies are broadly relevant and will facilitate the development of new therapy to combat dental caries and other diseases. PUBLIC HEALTH RELEVANCE: We have discovered that the primary causative agent of human dental caries, Streptococcus mutans, undergoes major changes in gene expression and dramatically remodels its surface in response to exposure to oxygen. The goals of this research are to understand how these changes affect the ability of this organism to colonize, persist and cause disease, and to dissect the underlying regulatory pathways that effect these changes. The knowledge generated from these studies will lead directly to new strategies to control dental caries and will provide much-needed insight into how other medically-important pathogens alter their appearance and behavior to cause diseases.