Molecular mechanism of V. vulnificus MARTX toxin in pathogenesis and food safety

创伤弧菌MARTX毒素发病机制及食品安全的分子机制

• 批准号: 8289407
• 负责人: Karla J F Satchell
• 金额: $ 38.13万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8289407
• 关键词: Accounting; Actins; Affect; Bacteria; Biochemical; Bioluminescence; CDC42 gene; Cause of Death; Cell Culture Techniques; Cell Death; Cell membrane; Cells; Cessation of life; Clinical; Consumption; Cytolysis; DNA Sequence Rearrangement; Data; Disease; Disease Progression; Epidemic; Epithelial; Factor V; Family; Flesh-Eating Bacteria; Food; Food Safety; Genetic; Global Warming; Growth; Guanosine Triphosphate Phosphohydrolases; Harvest; Hepatitis C; Histology; Hospitalization; Human; Image; Incidence; Industry; Infection; Intervention; Investigation; Knowledge; Lead; Lethal Dose 50; Link; Liver Cirrhosis; Liver Dysfunction; Maps; Marketing; Modeling; Molecular; Molecular Epidemiology; Molecular Mechanisms of Action; Necrosis; Necrotizing fasciitis; Oysters; Pathogenesis; Patients; Persons; Policies; Population; Process; Public Policy; Relative (related person); Research; Resistance; Role; Route; Safety; Seafood; Sepsis; Septicemia; Shellfish; Structure; System; Testing; Therapeutic; Tissues; Toxic effect; Toxin; Variant; Vibrio vulnificus; Virulence; Virulence Factors; Virulent; Work; base; coastal water; cytotoxic; cytotoxicity; domain mapping; gulf coast; immune clearance; in vivo; in vivo Model; macrophage; meetings; novel; pathogen; rho; surveillance strategy

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. Although infections are rare, the number of serious infections has been increasing in recent years, possibly due to global warming that has caused a rise in the number of days amenable to growth of V. vulnificus in coastal waters. 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, although its targets in vivo and molecular mechanism of action remain unknown. 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 disease due to consumption of contaminated food and identification and characterization of specific regions of the toxin linked to cell lysis and increased virulence potential.

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。虽然感染很少，但近年来严重感染的数量一直在增加，这可能是由于全球变暖导致沿海水域中创伤弧菌生长的天数增加。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，我们证明了这种毒素通过胃内感染途径与发病机制直接相关，尽管其体内靶点和分子作用机制尚不清楚。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。该提案的重点将是由于食用受污染的食物而直接影响疾病的机制，以及与细胞裂解和毒性潜力增加有关的毒素的特定区域的识别和表征。