A COMPARISON OF TWO STRAINS OF E COLI TO PRODUCE SEPTIC SHOCK IN DOGS

两种引起狗感染性休克的大肠杆菌菌株的比较

• 批准号: 6161407
• 负责人: C NATANSON
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6161407
• 关键词: Escherichia coli; Escherichia coli infections; bacterial toxins; blood toxicology; dogs; endotoxins; genetic manipulation; genetic strain; hemodynamics; septic shock; virulence

Summary of Work: While live bacteria commonly cause infection, the relative role of bacterial toxins versus live bacteria to produce morbidity and mortality is not known. If bacterial toxins are important factors, therapies directed at these toxins may be required. Even if no bacteria remain alive or grow, these preformed toxins may be important in determining morbidity and mortality. Therapies directed at these toxins may be important additions to antibiotic therapy. Using two strains of Escherichia coli, a nonvirulent E. coli strain (O86;H8) and a virulent E. coli strain (O6;Hl;K2), in the canine model, we designed a study to determine whether organism virulence factors or bacterial toxins were more important in producing septic shock. Measures of hemodynamic shock, blood cultures, endotoxin levels, and survival were done serially with both organisms live, both organisms killed, and with purified endotoxin from these organisms. Preliminary results from these studies have been presented to the American Federation of Clinical Research and the Society of Critical Care Medicine. The results suggested that virulence factors are much more important than preformed endotoxins for the development of endotoxemia. To further address this issue, we are collaborating with Tom Russo of LCI, MAID, and more recently the University of Buffalo, to examine the role of endotoxin as a virulence factor within the same of E. coli. We are using a gene disruption technique to produce an E. Coli strain with a deficiency in endotoxin O type side chains (another virulence factor). This will further explore the relative role of endotoxin in septic shock. Much work is presently being done to target this pathogen in human septic shock. There has been much interest in these results because the determination of the factors that produce morbidity in infection will guide trials for future therapies for children and adults with septic shock.

工作总结：虽然活细菌通常会导致感染，但 细菌毒素与活细菌产生的相对作用 发病率和死亡率尚不清楚。如果细菌毒素很重要 因素，针对这些毒素的治疗可能是必需的。即使不是 细菌保持存活或生长，这些预先形成的毒素可能是重要的 在确定发病率和死亡率方面。针对这些问题的治疗 毒素可能是抗生素治疗的重要补充。 使用两株大肠杆菌，一种无毒力的大肠杆菌菌株 (O86；H8)和一株强毒力大肠杆菌(O6；H1；K2)，在犬模型中， 我们设计了一项研究，以确定生物体毒力因素或 细菌毒素在感染性休克的发生中起更重要的作用。措施 血流动力学休克、血培养、内毒素水平和存活率 都是连续进行的，这两种生物都活着，两种生物都被杀死了，以及 从这些生物中提纯的内毒素。初步结果来自 这些研究已经提交给美国临床联合会。 研究和重症护理医学学会。结果是 表明毒力因素比预制的更重要 内毒素与内毒素血症的发展 为了进一步解决这个问题，我们正在与汤姆·鲁索合作 LCI，女佣，最近在布法罗大学，检查 内毒素在大肠杆菌中作为毒力因子的作用。我们 正在使用基因破坏技术来生产一种具有 内毒素O型侧链缺陷(另一个致病因素)。 这将进一步探讨内毒素在脓毒症中的相对作用。 令人震惊。目前正在做大量的工作来针对这种病原体 人类败血症休克。人们对这些结果很感兴趣 因为确定在中国引起发病率的因素 感染将指导儿童和成人未来治疗的试验 感染性休克。