The effect of inter-species interactions on the virulence of Streptococcus mutans

种间相互作用对变形链球菌毒力的影响

• 批准号: 7387549
• 负责人: Bing-Yan Wang
• 金额: $ 7.54万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-15 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7387549
• 关键词: Acids; Actinomyces naeslundii; Affect; Agar; Architecture; Attenuated; Bacteria; Biomass; Cell Count; Characteristics; Chronic; Communicable Diseases; Competence; Confocal Microscopy; Cysteine Protease; DNA; Data; Dental Plaque; Dental caries; Development; Disruption; Forsythia; Foundations; Genes; Genetic Transformation; Goals; Infective endocarditis; Interruption; Label; Lead; Mediating; Microbial Biofilms; Monitor; Morphology; Mutation; Numbers; Oncogenes; Organism; Parents; Peptides; Polystyrenes; Population; Porphyromonas gingivalis; Probiotics; Production; Property; Radioactive; Regulation; Signal Transduction; Streptococcus gordonii; Streptococcus mutans; Streptococcus mutans peptide competence factor; Surface; System; Techniques; Tetracycline; Tetracyclines; Treponema denticola; Virulence; Virulence Factors; Virulent; antimicrobial; arginyllysine; attenuation; bacteriocin; base; design; glucosyltransferase D; killings; mutant; novel therapeutics; oral bacteria; oral plaque; pathogen; proteinase P; quorum sensing; response

DESCRIPTION (provided by applicant): Project summary: Streptococcus mutans is the primary cariogen that produces several virulence factors. The long-term goal of the proposed studies is to characterize specific interactions of S. mutans with oral bacteria in the dental plaque biofilm. We hypothesize that it is not merely colonization by S. mutans that determines the ultimate cariogenicity of plaque, but the interaction of the pathogen with other biofilm bacteria that affect virulence. Other bacteria present in dental plaque may modulate quorum sensing-dependent expression of virulence properties of the organism. This hypothesis is based on observations that: 1) S. mutans competence-stimulating peptide (CSP) and a signal transduction system mediate a variety of virulence characteristics: biofilm formation, bacteriocin production, acid tolerance, antimicrobial sensitivity, and natural genetic transformation. Elimination of CSP or its signal transduction system results in alterations in all of these virulence activities. 2), other oral bacteria, such as the commensal early-colonizing dental plaque species Streptococcus gordonii, can inactivate S. mutans CSP thereby interfering with S. mutans bacteriocin production. Therefore, the experimental focus of this proposal will be to determine the effects of other early colonizers such as Actinomyces naeslundii and later anaerobic colonizers such as Porphyromonas gingivalis on quorum-sensing in S. mutans and to determine the effects of these organisms on the virulence-associated properties of S. mutans. The Specific Aims are: Specific Aim 1. To determine if early colonizers, S. gordonii or A. naeslundii, antagonize colonization efficiency and the acid tolerance response in S. mutans. i) Colonization of S. mutans WT and its comC mutant on preformed biofilms of S. gordonii Challis or A. naeslundii will be assessed by both radioactive labeling techniques and confocal microscopy. ii) The acid tolerance response of S. mutans and mixtures with S. gordonii Challis or A. naeslundii will be assessed by viable cell counts. Specific Aim 2. To determine if late colonizers such as P. gingivalis, Treponema denticola, and Tannerella forsythia antagonize quorum-sensing properties in S. mutans. i) S. mutans bacteriocin production in broth monocultures of S. mutans and mixtures of S. mutans with P. gingivalis, T. denticola, or T. forsythia will be monitored by determining killing percentages of an indicator strain. ii) The transformation efficiencies of S. mutans in monocultures and in mixtures with P. gingivalis, T. denticola, or T. forsythia will be assessed. iii) The acid tolerance response of S. mutans and mixtures with P. gingivalis, T. denticola, or T. forsythia will be assessed by viable cell counts. iv) We will determine if the proteinases of P. gingivalis inactivate the S. mutans CSP. Project Narrative: Dental caries is a common chronic infectious disease affecting much of the worldwide population. The S. mutans quorum-sensing system may be an appropriate target for interruption to reduce dental caries. The disruption of CSP-dependent regulation has the potential to attenuate the bacterium so that it is less virulent.

描述（由申请人提供）： 项目摘要：变形链球菌是产生多种毒力因子的主要致龋菌。拟议研究的长期目标是表征变形链球菌与牙菌斑生物膜中口腔细菌的特定相互作用。我们假设，决定斑块最终致龋性的不仅仅是变形链球菌的定殖，而且病原体与影响毒力的其他生物膜细菌的相互作用。牙菌斑中存在的其他细菌可能会调节生物体毒力特性的群体感应依赖性表达。该假设基于以下观察：1) 变形链球菌能力刺激肽 (CSP) 和信号转导系统介导多种毒力特征：生物膜形成、细菌素产生、酸耐受性、抗菌敏感性和自然遗传转化。消除 CSP 或其信号转导系统会导致所有这些毒力活动发生改变。 2)，其他口腔细菌，例如共生的早期定植牙菌斑物种戈登链球菌，可以使变形链球菌 CSP 失活，从而干扰变形链球菌细菌素的产生。因此，本提案的实验重点将是确定其他早期定殖者（例如内氏放线菌）和后来的厌氧定殖者（例如牙龈卟啉单胞菌）对变形链球菌群体感应的影响，并确定这些生物体对毒力的影响。变形链球菌的相关特性。具体目标是： 具体目标 1. 确定早期定殖者（S. gordonii 或 A. naeslundii）是否会拮抗变形链球菌的定殖效率和耐酸反应。 i)将通过放射性标记技术和共聚焦显微镜来评估S.mutans WT及其comC突变体在S.gordonii Challis或A.naeslundii的预形成生物膜上的定殖。 ii) S. mutans 以及与 S. gordonii Challis 或 A. naeslundii 的混合物的耐酸反应将通过活细胞计数进行评估。具体目标 2. 确定晚期定殖菌（例如牙龈卟啉单胞菌、齿垢密螺旋体和连翘坦纳菌）是否会拮抗变形链球菌的群体感应特性。 i)通过测定指示菌株的杀灭百分比来监测变形链球菌的肉汤单一培养物以及变形链球菌与牙龈卟啉单胞菌、齿垢毛霉或连翘毛霉的混合物中的变形链球菌细菌素生产。 ii) 将评估变形链球菌在单一培养物中以及与牙龈卟啉单胞菌、齿垢链球菌或连翘链球菌的混合物中的转化效率。 iii) 变形链球菌以及与牙龈卟啉单胞菌、齿形链球菌或连翘链球菌的混合物的耐酸反应将通过活细胞计数来评估。 iv) 我们将确定牙龈卟啉单胞菌的蛋白酶是否会使变形链球菌 CSP 失活。 项目叙述：龋齿是一种常见的慢性传染病，影响着全世界大部分人口。变形链球菌群体感应系统可能是减少龋齿的适当干扰目标。 CSP 依赖性调节的破坏有可能减弱细菌的毒性，从而降低其毒性。