Function of Vibrio vulnificus MARTX toxin during early gut infection

描述（由申请人提供）：创伤弧菌是沿海沃茨的自然居民，包括美国海湾。这种细菌在食用受污染的海鲜（特别是生牡蛎）后会导致快速败血症，主要发生在肝功能障碍的人身上。在食物来源的病原体中，创伤弧菌以其高住院率和死亡率而闻名。事实上，V. vulnificus占食物源性疾病死亡人数的1%，尽管仅引起0.003%的疾病。FDA试图通过实施收获后处理规定来保护消费者，但遭到了贝类收获行业的强烈抵制，迫使FDA审查其政策。因此，研究创伤弧菌的发病机制已成为食品安全和公共政策的优先事项。最近的研究表明，创伤弧菌的细胞毒性主要与一种大的多功能自处理RTX毒素（MARTXVv）有关。在这项研究中，我们证明，这种毒素是直接联系到发病机制的胃内途径的感染。我们建议使用体内、细胞培养和生化系统研究MARTXVv毒素在发病机制中的作用。该提案的重点将是食用受污染食物后直接影响早期感染的机制，以及与组织损伤和免疫系统逃避有关的毒素特定区域的识别和表征。 公共卫生相关性：创伤弧菌是一种细菌，栖息在美国海湾，并导致败血症和坏死性筋膜炎（食肉细菌）。这项关于创伤弧菌发病机制的研究将具体描述细菌分泌的毒力因子，该因子与食用受污染食物（特别是牡蛎）后的疾病有关。完成后，这项研究将确定如何这个因素有助于食物伯恩感染。

DESCRIPTION (provided by applicant): Vibrio vulnificus is a natural inhabitant of coastal waters, including the US Gulf. The bacterium causes rapid septicemia after consumption of contaminated seafood (especially raw oysters), predominantly in persons with liver dysfunction. Among food-bourne pathogens, V. vulnificus is most notable for its high rates of hospitalization and death. Indeed, V. vulnificus accounts for 1% of deaths from food-bourne illness despite causing only 0.003% of illnesses. Attempts by the FDA to protect consumers by implementation of post- harvest processing mandates met with significant resistance from the shellfish harvesting industry forcing the FDA to review its policies. Thus, the study of V. vulnificus pathogenesis has become a food safety and public policy priority. Recent studies establish that cytotoxicity of V. vulnificus is predominantly associated with a large Multifunctional-Autoprocessing RTX toxin (MARTXVv). In this study, we demonstrate that this toxin is directly linked to pathogenesis by the intragastric route of infection. We propose to study the role of the MARTXVv toxin in pathogenesis using in vivo, cell culture, and biochemical systems. The focus of the proposal will be mechanisms directly impacting early infection after consumption of contaminated food and identification and characterization of specific regions of the toxin linked to tissue damage and immune system evasion. PUBLIC HEALTH RELEVANCE: Vibrio vulnificus is a bacterium that inhabits the US Gulf and causes sepsis and necrotizing fasciitis (flesh- eating bacteria). This study of V. vulnificus pathogenesis will specifically characterize a virulence factor secreted by the bacterium that is linked to disease after consumption of contaminated food (especially oysters). When completed, this study will define how this factor contributes to food bourne infection.