Streptococcal-Zebrafish Model of Bacterial Pathogenesis

细菌发病机制的链球菌-斑马鱼模型

• 批准号: 6703705
• 负责人: MELODY Neuhart NEELY
• 金额: $ 25.95万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-02-15 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6703705
• 关键词: Streptococcus; Streptococcus infection; Streptococcus pyogenes; bacteria infection mechanism; bacterial cytopathogenic effect; bacterial genetics; bacterial proteins; gene expression; gene induction /repression; gene interaction; genetic strain; histopathology; host organism interaction; pathologic process; polymerase chain reaction; protein structure function; virulence; zebrafish

DESCRIPTION (provided by applicant): Streptococcal pathogens continue to evade concerted efforts to decipher clear-cut virulence mechanisms, although numerous genes have been implicated in pathogenesis. A single species can infect a diversity of tissues, suggesting the expression of specific virulence factors based on the local tissue environment or stage of infection. Our long-range goal is to identify the interactions that occur between the host and pathogen that lead to activation of virulence mechanisms and contribute to specific streptococcal disease states. The objective of this application is to characterize specific virulence mechanisms utilized within various tissues in vivo by employing a unique animal model, the zebrafish (Danio rerio). We will accomplish this by studying infection by two streptococcal species that represent two forms of streptococcal disease: a natural pathogen of both fish and humans, Streptococcus iniae, and a human-specific pathogen, Streptococcus pyogenes. While S. iniae primarily causes systemic disease in the zebrafish following intra-muscular injection, S. pyogenes causes a locally spreading necrotic disease confined to the muscle. By studying pathogens that are virulent for both fish and humans and that mediate disease states in the zebrafish that are identical to those found in human streptococcal infections, we will be able to identify common virulence strategies shared by a number of Gram positive pathogens. The central hypothesis is that streptococcal pathogens respond to their host by initiating specific virulence mechanisms based on the local tissue environment or host-specific factors expressed within that tissue. We propose to: (1) identify and characterize bacterial proteins that interact with the host in vivo to cause specific disease states and (2) characterize the role in pathogenesis of proteins previously implicated in virulence.

描述（由申请人提供）：尽管许多基因与发病机理有关，但链球菌病原体继续逃避了破译清晰毒力机制的协同努力。一个物种可以感染各种组织，表明基于局部组织环境或感染阶段的特定毒力因子的表达。我们的远程目标是确定宿主与病原体之间发生的相互作用，导致毒力机制激活并有助于特定的链球菌疾病状态。该应用的目的是通过采用独特的动物模型，斑马鱼（Danio Rerio）来表征体内各种组织中使用的特定毒力机制。我们将通过研究两种代表两种形式的链球菌疾病的链球菌感染来实现这一目标：鱼类和人类的天然病原体，iniae链球菌和一种人类特异性的病原体，链球菌链球菌。 s. iniae主要在斑马内注射后在斑马鱼中引起全身性疾病，而链球菌则导致局部扩散的坏死性疾病，局限于肌肉。通过研究针对鱼类和人类有毒的病原体，并介导斑马鱼中的疾病状态与在人类链球菌感染中发现的病原体相同，我们将能够鉴定出许多革兰氏阳性病原体共享的常见毒力策略。中心假设是，链球菌病原体通过基于局部组织环境或该组织中表达的宿主特异性因素启动特定的毒力机制来反应其宿主。我们建议：（1）识别和表征与体内与宿主相互作用的细菌蛋白，以引起特定的疾病状态，（2）表征先前与毒力有关的蛋白质发病机理中的作用。