E COLI VIRULENCE TRAITS IN INTRAABDOMINAL INFECTION

尽管外科技术有了进步，重症监护设施， 诊断能力，以及抗菌治疗的改进， 腹内感染的死亡率仍然很高。最近的一次经历 来自五所大学重症监护病房的报告称，总死亡率为 28%死于腹内感染。临床问题的严重性 这就需要继续进行基础研究。腹膜腔内有一个 卓越的抗击感染能力。外科前辈们已经奠定了 定义身体这一区域的力学基础 处理感染问题。这些通常被描述为：a)快速扩散 通过横隔膜淋巴管传播颗粒物(包括细菌) 腔隙；b)腹膜内吞噬能力的快速上调 在细菌进入后2-6小时内；以及c)机械 用纤维蛋白捕捉法和死腔封闭法隔离细菌 瘫痪的肠梗阻。多数人忽略的一项重要考虑 这些研究中的一项是基于快速预测结果的变化 感染生物的适应性变化。不是所有的细菌都有 同样的能力会产生感染，许多人可能会经历显著的 不同环境中的表型变化。这样做的具体目的是 建议是了解最频繁地从细菌中恢复的细菌 腹内感染，大肠杆菌，在腹膜过程中进化 感染。这些有机体不是惰性的，而是主动地改变它们的 在敌意环境中生存的代谢途径和物理特性 环境。该项目的目标是确定：1) 不同野生型和不同实验室菌株E。 并将已知的毒力性状(O和K抗原， 甲型溶血素的产生，与哺乳动物细胞的黏附能力，以及 外膜蛋白的表达)对植物体内的生存能力的影响 腹膜。2)佐剂对腹膜腔感染的影响 (血红蛋白、胆盐、粪便、粘蛋白)对大肠杆菌和 与毒力的相关性。3)大肠埃希菌促进混合培养的特性 感染：尤其是最常见的厌氧菌类杆菌 脆弱的。改善腹内感染患者的预后 当医生不仅了解宿主的方式 防御与感染的有机体相互作用，但也与适应性 细菌在宿主腹膜内生存的机制。 这项提议的目的是开始划定 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.