Function of Vibrio vulnificus MARTX toxin during early gut infection

描述（由申请人提供）：创伤弧菌是沿海水域的自然居民，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）后会引起快速败血症，主要发生在肝功能不全的人身上。在食源性致病菌中，创伤弧菌以其高住院率和死亡率最为显著。事实上，创伤弧菌占食源性疾病死亡人数的1%，尽管仅引起0.003%的疾病。FDA试图通过实施捕捞后加工指令来保护消费者，但遭到了贝类捕捞行业的强烈抵制，迫使FDA重新审视其政策。因此，对创伤弧菌发病机制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个大的多功能自动加工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机制直接相关。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。该提案的重点将是直接影响食用受污染食品后早期感染的机制，以及与组织损伤和免疫系统逃避相关的毒素特定区域的识别和表征。

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.