The Snm secretion system in Mycobacterium smegmatis

描述（由申请人提供）：许多致病菌，包括结核分枝杆菌，使用独立于sec的分泌途径分泌效应蛋白来操纵宿主细胞，以便在感染期间生长和持续存在。在结核分枝杆菌中，Snm（分枝杆菌分泌）系统是产生毒力所必需的，它由两种已知底物易位所需的三个组成部分组成。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进一步表征Snm系统。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分泌系统的成分和调节因子的突变体也将从基因上进行鉴定。最后，将通过与遗传易感的土壤变形虫Dictyostelium discoideum和Acanthamoeba castellanii建立相互作用模型，探讨Snm系统在M. sme垢垢菌中的生物学作用。

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.