Function of Vibrio vulnificus MARTX toxin during early gut infection

描述(申请人提供)：创伤弧菌是沿海水域的天然居民，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)后会导致迅速败血症，主要发生在有肝功能障碍的人身上。在食源性致病菌中，创伤弧菌以其较高的住院率和死亡率而闻名。事实上，创伤弧菌占食物伯恩病死亡的1%，尽管只有0.003%的疾病是由创伤弧菌引起。FDA试图通过实施收获后加工任务来保护消费者，但遭到了贝类捕捞行业的强烈抵制，迫使FDA审查其政策。因此，创伤弧菌致病机理的研究已成为食品安全和公共政策的重点。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动处理RTX毒素(MARTXVv)有关。在这项研究中，我们证明这种毒素通过胃内感染途径与发病直接相关。我们建议利用体内、细胞培养和生化系统来研究MARTXVv毒素在发病机制中的作用。该提案的重点将是在食用受污染的食物后直接影响早期感染的机制，以及确定和表征与组织损伤和免疫系统逃避有关的毒素的特定区域。

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.