The Snm secretion system in Mycobacterium smegmatis

描述(申请人提供)：许多致病细菌，包括结核分枝杆菌，使用SEC非依赖的分泌途径来分泌效应蛋白，以操纵宿主细胞，以便在感染期间生长并持续存在。在结核分枝杆菌中，SNM(分枝杆菌分泌物)系统是毒力所必需的，它由两种已知底物转运所需的三种成分组成。目前的假设是SNM途径是细菌操纵真核吞噬细胞的保守系统。由于这种新的分泌系统在非致病土壤细菌污垢分枝杆菌中是保守的，因此将使用这种分枝杆菌对SNM系统进行进一步的表征。遗传和生化方法将用于鉴定SNM分泌系统的其他底物，并确定这些底物共有的分泌信号。SNM分泌系统的组成部分和调节器中的突变也将从基因上确定。最后，将通过开发一个与遗传易驯化的土壤阿米巴、盘状阿米巴和卡氏棘阿米巴的相互作用模型来探索SNM系统在耻垢分枝杆菌中的生物学作用。

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.