TRANSLOCATING BACTERIA: ROLE IN POSTSURGICAL SEPSIS

在美国，革兰氏阴性菌血症的发病率各不相同 每年有71,000到330,000个病例，但尽管在 抗菌治疗，与革兰氏阴性相关的死亡率 菌血症(包括术后败血症)保持在20%至50%之间。 (1)。有证据表明，肠道细菌的移位会导致 有相当大比例的并发感染(包括败血症) 住院免疫抑制患者、手术后患者和创伤 患者(2)。正常肠道细菌可引发全身性疾病 通过组织学上完整的肠粘膜移位，但是 细菌传播的途径和机制仍然难以捉摸。 由于肠道的复杂动力学。最近的活体实验 研究表明，细菌可以转移到排水口 组织巨噬细胞内的肠系膜淋巴结(17，20-21,117)，以及 易位粪肠球菌(9)和白色念珠菌(17) 定位于完整的肠上皮细胞。初级阶段 这项建议的目的是澄清细菌中的初始事件 通过完整的肠粘膜移位。来自体内的结果 小鼠模型与体外实验结果相关 涉及移位细菌与培养物之间的相互作用 肠上皮细胞和单核吞噬细胞。九 不同的细菌菌株以不同的频率移位 (坦率地说，高频率易位的致病菌株 [鼠伤寒沙门氏菌，单核细胞增生性李斯特菌]，兼性菌株 以中频移位[大肠杆菌、变形杆菌 奇异杆菌、粪肠球菌]、罕见的厌氧菌 易位[脆弱类杆菌])在常规饲养的 和无菌小鼠；易位通过定量监测 微生物方法，以及光、免疫荧光和 用电子显微镜方法观察血管内皮细胞生长途径 肠粘膜内的移位。这些活体结果是 与体外实验的结果相关，这些实验旨在解剖 相互作用中涉及的因素(粘着、吸收、 细胞内存活)这些细菌菌株与培养 肠细胞和单核巨噬细胞。体外和体外实验的结果 活体实验可以通过相互关联来阐明 细菌感染过程中的肠细胞和组织巨噬细胞 易位。这一方法不仅将使路线清晰，而且 参与细菌移位的机制，但也应(A) 有助于我们了解肠道的正常功能 细胞；(B)阐明肠细胞作为非专业人士的作用 吞噬细胞；(C)阐明正常肠道细菌与 组织巨噬细胞；(D)扩大我们对细菌毒力的知识 细胞一级的机制；(E)很可能是新的 减少与以下疾病相关的昂贵发病率的治疗方案 细菌移位引起的全身性感染。

In the United States, the incidence of gram-negative bacteremia varies between 71,000 and 330,000 cases per year, but despite the advances in antimicrobial therapy, the mortality associated with gramnegative bacteremia (including postsurgical sepsis) remains between 20% and 50% (1). There is evidence that translocating intestinal bacteria cause a significant proportion of complicating infections (including sepsis) in hospitalized immunosuppressed patients, postsurgical patients, and trauma patients (2). Normal intestinal bacteria can initiate systemic disease by translocating through a histologically intact intestinal mucosa, but the routes and mechanisms of bacterial transport have remained elusive due to the complex dynamics of the intestinal tract. Recent in vivo studies have indicated that bacteria can translocate to the draining mesenteric lymph node within tissue macrophages (17, 20-21,117), and translocating Enterococcus faecalis (9) and Candida albicans (17) have been localized within intact intestinal epithelial cells. The primary aim of this proposal is to clarify the initial events in bacterial translocation through an intact intestinal mucosa. Results from in vivo mouse model are correlated with results from in vitro experiments involving the interactions of translocating bacteria with cultured intestinal epithelial cells and with mononuclear phagocytes. Nine different bacterial strains that translocate with varying frequencies (frankly pathogenic strains that translocate with high frequency [Salmonella typhimurium, Listeria monocytogenes], facultative strains that translocate with intermediate frequency [Escherichia coli, Proteus mirabilis, Enterococcus faecalis], anaerobic strains that rarely translocate [Bacteroides fragilis]) are studied in conventionally reared and germfree mice; translocation is monitored by quantitative microbiological methods, as well as light, immunofluorescent, and electron microscopic methods for visualization of the route of translocation within the intestinal mucosa. These in vivo results are correlated with the results of in vitro experiments designed to dissect the factors involved in the interactions (adherence, uptake, intracellular survival) of these bacterial strains with cultured enterocytes and with mononuclear phagocytes. The results of in vitro and in vivo experiments can be correlated to clarify the roles of the enterocyte and the tissue macrophage in the process of bacterial translocation. This approach will not only clarity the routes and mechanisms involved in bacterial translocation, but should also (a) contribute to our understanding of the normal function of intestinal cells; (b) elucidate the role of the enterocyte as a nonprofessional phagocyte; (c) clarify the interactions of normal enteric bacteria with tissue macrophages; (d) expand our knowledge of bacterial virulence mechanisms at the cellular level; (e) suggest, most likely, new treatment regimens to decrease the costly morbidity associated with systemic infections caused by translocating bacteria.