The Snm secretion system in Mycobacterium smegmatis

耻垢分枝杆菌的 Snm 分泌系统

• 批准号: 7482351
• 负责人: Patricia A Champion
• 金额: $ 5.2万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7482351
• 关键词: Acanthamoeba castellanii; Amoeba genus; Bacteria; Biochemical Genetics; Biological; Cells; Development; Dictyostelium discoideum; Genus Mycobacterium; Infection; Modeling; Mycobacterium smegmatis; Mycobacterium tuberculosis; Pathway interactions; Phagocytes; Proteins; Role; Signal Transduction; Soil; System; Virulence; mutant; mycobacterial; novel; pathogenic bacteria

DESCRIPTION (provided by applicant): Many pathogenic bacteria, including M. tuberculosis, secrete effector proteins using Sec-independent secretion pathways to manipulate host-cells in order to grow and persist during infection. In M. tuberculosis, the Snm (secretion in mycobacteria) system is required for virulence and consists of three components required for the translocation of two known substrates. The current hypothesis is that the Snm pathway is a conserved system by which bacteria manipulate eukaryotic phagocytes. Because this novel secretion system is conserved in the non-pathogenic soil bacterium Mycobacterium smegmatis, further characterization of the Snm system using this mycobacterial species will be performed. Both genetic and biochemical approaches will be used to identify other substrates of the Snm secretion system and to determine a secretion signal common to these substrates. Mutants in components and in regulators of the Snm secretion system will also be identified genetically. Finally, the biological role of the Snm system in M. smegmatis will be explored through the development of an interaction model with the genetically tractable soil amoebae Dictyostelium discoideum and Acanthamoeba castellanii.

性状（由申请人提供）：许多致病菌，包括M。结核病，分泌效应蛋白使用Sec-非依赖性分泌途径操纵宿主细胞，以便在感染期间生长和持续。In M.在结核病中，毒力需要Snm（分枝杆菌中的分泌）系统，并且该系统由两种已知底物的易位所需的三种组分组成。目前的假设是，Snm途径是一个保守的系统，细菌操纵真核吞噬细胞。由于这种新的分泌系统在非致病性土壤细菌耻垢分枝杆菌中是保守的，因此将使用这种分枝杆菌物种对Snm系统进行进一步表征。遗传和生物化学方法将用于识别Snm分泌系统的其他底物，并确定这些底物共同的分泌信号。还将从遗传学上鉴定Snm分泌系统的组分和调节剂中的突变体。最后，对Snm系统在M.将通过与遗传上易处理的土壤阿米巴Dictyosteelium discoideum和Castellanii阿米巴的相互作用模型的开发来探索smegelium。