Escape of intracellular Shigella from autophagy

Speaker：Jung-Yen Liu

Commentator：Dr. Jing-Jou Yan

             Time：2005/04/20

             Place：Room 601

Shigella flexneri is an invasive pathogen of the gut that causes shigellosis, an acute infections colitis that is a major pediatric issue worldwide. In the previous, Ogawa et al had characterized the icsB mutants remained invasive, but formed abnormally small plaques on BHK cell monolayers. And the real function of IcsB, which is one of effector proteins secreted by Shigella via the type III secretion system, isn’t known until now. For further understanding its function, they show that the mutant strains are trapped within autophagosome and bacterial survival is affected. In the atg5^-/- cells, deficient in formation of autophagy, the mutant strains can recover replication ability. However, in the pull down assay, icsB doesn’t interact with autophagic proteins. Unusually Ogawa et al note that autophagosome markers, autophagic membranes and atg5 tend to be located at one end of bacterium, as the distribution of another effector protein, VirG. Indeed, Atg5 has affinity with VirG. In addition, in the presence of IcsB, VirG cannot bind to atg5 and in a dose-dependent manner. Furthermore, virG itself can triggers autophagy. In a word, the authors find shigella prevents VirG becoming the target for autophagy by secreting icsB. This finding is clinically relevant because the discovery of pathogen molecules that inhibit autophagy-mediated recognition may lead to the generation of new vaccines.

Reference：

1.      Robbins, J. R. et al. The making of a gradient: IcsA（VirG）polarity in shigella flexneri. Mol. Microbiol. 41, 861, 2001

2.      Ogawa, M. et al. IcsB: secreted via the type III secretion system is chaperoned by IpgA and required at the post-invasion stage of Shigellapathogenesity. Mol. Microbiol. 48, 913, 2003

3.      Ogawa, M. et al. Escape of intracellular Shigella from autophagy. Science. 307, 727, 2005

4.