Cooperative pathogenicity of enteropathogenic E. coli (EPEC) within mucosa-attached microcolonies

粘膜附着微菌落内致病性大肠杆菌 (EPEC) 的协同致病性

• 批准号: 504049752
• 负责人: Dr. Aline Dupont, Ph.D.
• 金额: --
• 依托单位: Institut für Medizinische Mikrobiologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/504049752?language=en
• 关键词: Cooperative; pathogenicity; enteropathogenic; E.; coli

Dynamic multicellular bacterial consortia intimately attached to the host’s small intestinal mucosal surface represent the hallmark of enteropathogenic E. coli (EPEC) pathogenicity. Despite their fundamental importance, the structural and spatial organization and the transcriptional heterogeneity, cooperative activity and communication between individual bacteria within these heterogeneous multicellular consortia have not yet been analyzed. Here, we therefore propose to employ established in vitro, ex vivo and in vivo models in combination with genetic reporter technology, competition experiments with isogenic EPEC mutants, highly innovative bacterial single cell transcriptomics and advanced imaging technologies to study the overall structural organization and functional interaction between bacteria, characterize the transcriptional heterogeneity within these consortia, and identify the mechanisms that underlie and account for the cooperative pathogenicity of EPEC. If successful, the obtained results are expected to significantly advance our understanding of the cooperative action of bacteria within multicellular consortia and its critical contribution to EPEC colonization, transmission and pathogenesis.

动态多细胞细菌聚生体紧密附着于宿主小肠粘膜表面是肠致病性大肠杆菌的标志。大肠杆菌（EPEC）的致病性。尽管它们具有根本的重要性，但这些异质多细胞聚生体内单个细菌之间的结构和空间组织以及转录异质性、合作活动和通讯尚未得到分析。因此，我们建议采用已建立的体外、离体和体内模型，结合遗传报告基因技术、同基因EPEC突变体竞争实验、高度创新的细菌单细胞转录组学和先进的成像技术来研究细菌之间的整体结构组织和功能相互作用，表征这些聚生体内的转录异质性，并确定的基础和说明合作致病性的EPEC的机制。如果成功的话，所获得的结果预计将显着推进我们的多细胞聚生体内的细菌的合作行动和它的关键贡献EPEC定植，传输和发病机制的理解。