E COLI VIRULENCE TRAITS IN INTRAABDOMINAL INFECTION

尽管外科技术，重症监护设施， 诊断能力，以及抗菌治疗的改进， 腹腔内感染的死亡率仍然很高。 最近的经验 来自五所大学重症监护病房的报告显示， 腹腔感染占28%。 临床问题的严重性 需要继续进行基础研究。 腹膜腔具有 抵抗感染的非凡能力 外科前辈们已经奠定了 定义身体这个区域的机制的基础 处理感染。 这些通常被描述为：a）快速分散 颗粒物（包括细菌）的吸附 陷窝; B）腹膜内吞噬能力的快速上调 在细菌引入后2-6小时内;和c）机械的 通过纤维蛋白捕获和死腔闭塞隔离细菌 麻痹性肠梗阻 大多数人缺少的一个重要考虑因素是， 这些研究中的一项是， 感染生物的适应性变化。 并非所有细菌都具有 同样的能力，产生感染，许多人可以经历重大的 不同环境下的表型变化。 其具体目的是 建议是了解如何最频繁地回收细菌从 腹腔内感染，大肠杆菌，在腹膜 感染 这些生物不是惰性的，而是积极地改变它们的 代谢途径和物理特性，以在敌对环境中生存， 环境 该项目的目标是确定：1） 不同野生型和实验室菌株的E. 大肠杆菌，并关联已知的毒力性状（O和K抗原， α-溶血素的产生，粘附哺乳动物细胞的能力，以及 外膜蛋白的表达）与细胞内存活率之间的关系。 腹膜 2)腹腔感染佐剂的作用 （血红蛋白、胆汁盐、粪便、粘蛋白）对E.杆菌和 与毒力的相关性 3)E.大肠杆菌，促进混合 感染：特别是最常见的厌氧菌，拟杆菌 脆弱的 改善腹腔感染患者的预后 当医生不仅了解宿主 防御与感染生物相互作用，但适应性 细菌在宿主腹膜内生存的机制。 本提案的目的是开始划定 这些机制。

In spite of advances in surgical techniques, critical care facilities, diagnostic capacities, and improvements in antimicrobial therapy, the mortality from intraabdominal infection remains high. A recent experience from five university intensive care units reported an overall mortality of 28% from intraabdominal infection. The magnitude of the clinical problem necessitates continued basic research. The peritoneal cavity possesses a remarkable capacity to combat infection. Surgical predecessors have laid the groundwork of defining the mechanics whereby this region of the body handles infection. These are typically described as: a) rapid dispersal of particulate matter (including bacteria) via diaphragmatic lymphatics lacunae; b) rapid upregulation of phagocytic capacity within the peritoneum within 2-6 hours after bacterial introduction; and c) mechanical sequestration of bacteria by fibrin trapping and obliteration of dead space by paralytic ileus. An important consideration missing from the majority of these studies is the alteration in outcome predicated upon rapid adaptive changes of the infecting organisms. All bacteria do not possess the same ability to produce infection and many can undergo significant phenotypic changes in different environments. The specific aim of this proposal is to understand how the most frequently recovered bacteria from intraabdominal infection, Escherichia coli, evolves during peritoneal infection. These organisms are not inert, but actively change their metabolic pathways and physical properties to survive in a hostile environment. The goals of the project are to determine: 1) the intraperitoneal kinetics of varying wild types and laboratory strains of E. coli, and correlate known virulence traits (O and K antigens, alpha-hemolysin production, ability to adhere to mammalian cells, and the expression of outer membrane proteins) to survivability within the peritoneum. 2) the effect of adjuvants of intraperitoneal infection (hemoglobin, bile salts, stool, mucin) upon the infectivity of E. coli and correlation with virulence. 3) the traits of E. coli which promote mixed infections: in particular with the most common anaerobe, Bacteroides fragilis. An improved prognosis for patients with intraabdominal infection will occur when physicians understand not only the manner in which the host defenses interact with infecting organisms, but also the adaptive mechanisms employed by the bacteria to survive within the host peritoneum. It is the purpose of this proposal to begin the process of delineating these mechanisms.