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

工作总结：虽然活细菌通常会引起感染， 细菌毒素与活细菌的相对作用， 发病率和死亡率未知。如果细菌毒素很重要 由于这些因素，可能需要针对这些毒素的治疗。即使没有 细菌仍然活着或生长，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。针对这些疾病的治疗 毒素可能是抗生素治疗的重要补充。 用两株大肠杆菌，从大肠杆菌中分离到一株无毒的大肠杆菌。杆菌菌株 (O86 H8）和一株强毒E.大肠杆菌菌株（O 6; H1;K2），在犬模型中， 我们设计了一项研究，以确定生物体的毒力因子或 细菌毒素在产生感染性休克中更重要。措施 血液动力学休克，血培养，内毒素水平， 两种生物都活了，两种生物都死了， 从这些微生物中提纯的内毒素的初步结果 这些研究已提交给美国临床医学联合会， 研究和重症监护医学协会。结果 表明毒力因子比预先形成的要重要得多， 内毒素导致内毒素血症。 为了进一步解决这个问题，我们正在与汤姆·罗素合作， LCI，MAID，以及最近的布法罗大学，研究了 内毒素在大肠杆菌中作为毒力因子的作用。杆菌我们 正在使用基因破坏技术来生产E.大肠杆菌菌株， 内毒素O型侧链（另一种毒力因子）缺乏。 这将进一步探讨内毒素在脓毒症中的相对作用。 冲击.目前正在做大量工作来靶向这种病原体， 人类败血性休克人们对这些结果很感兴趣 因为确定导致发病的因素， 感染将指导未来儿童和成人治疗的试验 感染性休克

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.