Antão Esther-Maria, Glodde Susanne, Li Ganwu, Sharifi Reza, Homeier Timo, Laturnus Claudia, Diehl Ines, Bethe Astrid, Philipp Hans-C, Preisinger Rudolf, Wieler Lothar H, Ewers Christa
Institute of Microbiology and Epizootics, Freie Universität Berlin, Philippstrasse 13, 10115 Berlin, Germany.
Microb Pathog. 2008 Nov-Dec;45(5-6):361-9. doi: 10.1016/j.micpath.2008.08.005. Epub 2008 Sep 20.
E. coli infections in avian species have become an economic threat to the poultry industry worldwide. Several factors have been associated with the virulence of E. coli in avian hosts, but no specific virulence gene has been identified as being entirely responsible for the pathogenicity of avian pathogenic E. coli (APEC). Needless to say, the chicken would serve as the best model organism for unravelling the pathogenic mechanisms of APEC, an extraintestinal pathogen. Five-week-old white leghorn SPF chickens were infected intra-tracheally with a well characterized APEC field strain IMT5155 (O2:K1:H5) using different doses corresponding to the respective models of infection established, that is, the lung colonization model allowing re-isolation of bacteria only from the lung but not from other internal organs, and the systemic infection model. These two models represent the crucial steps in the pathogenesis of APEC infections, including the colonization of the lung epithelium and the spread of bacteria throughout the bloodstream. The read-out system includes a clinical score, pathomorphological changes and bacterial load determination. The lung colonization model has been established and described for the first time in this study, in addition to a comprehensive account of a systemic infection model which enables the study of severe extraintestinal pathogenic E. coli (ExPEC) infections. These in vivo models enable the application of various molecular approaches to study host-pathogen interactions more closely. The most important application of such genetic manipulation techniques is the identification of genes required for extraintestinal virulence, as well as host genes involved in immunity in vivo. The knowledge obtained from these studies serves the dual purpose of shedding light on the nature of virulence itself, as well as providing a route for rational attenuation of the pathogen for vaccine construction, a measure by which extraintestinal infections, including those caused by APEC, could eventually be controlled and prevented in the field.
禽类中的大肠杆菌感染已成为全球家禽业的经济威胁。有几个因素与禽类宿主中大肠杆菌的毒力有关,但尚未确定有任何特定的毒力基因完全负责禽致病性大肠杆菌(APEC)的致病性。毋庸置疑,鸡将是阐明APEC(一种肠道外病原体)致病机制的最佳模式生物。使用对应于已建立的各自感染模型的不同剂量,对5周龄的白来航SPF鸡进行气管内接种,接种的是一株特征明确的APEC田间菌株IMT5155(O2:K1:H5),即肺定植模型(仅允许从肺而不是其他内部器官重新分离细菌)和全身感染模型。这两种模型代表了APEC感染发病机制中的关键步骤,包括肺上皮的定植和细菌在整个血流中的传播。读出系统包括临床评分、病理形态学变化和细菌载量测定。除了全面描述能够研究严重肠道外致病性大肠杆菌(ExPEC)感染的全身感染模型外,本研究还首次建立并描述了肺定植模型。这些体内模型能够应用各种分子方法更密切地研究宿主-病原体相互作用。这种基因操作技术最重要的应用是鉴定肠道外毒力所需的基因,以及体内参与免疫的宿主基因。从这些研究中获得的知识具有双重目的,既有助于阐明毒力本身的性质,又为合理减毒病原体用于疫苗构建提供了一条途径,通过这一措施,最终可以在现场控制和预防包括APEC引起的肠道外感染。