Editor’s Choice: How Shigella hijacks the lysosome

Posted on September 15, 2021   by Microbiology Society

In this blog, Dr Ryan Hunter discusses ‘Shigella escapes lysosomal degradation through inactivation of Rab31 by IpaH4.5’ which he selected as Editor’s Choice in the Journal of Medical Microbiology after its publication in July.

Shigella flexneri is an intracellular bacterial pathogen that uses a type III secretion apparatus to inject effector proteins into host cells to aid the pathogen to invade said host. This study aimed to reveal the mechanisms and specific target within the host cell of the effector protein, named IpaH4.5, as well as its role in S. flexneri infection. The researchers identified that IpaH4.5 conteracts the hosts ability to fight infection by disrupting lysosmal function.

Shigella escapes lysosomal degradation through inactivation of Rab31 by IpaH4.5

Shigella flexneri is an intracellular pathogen of the colonic epithelium, resulting in bacillary dysentery and a significant public health burden. While its pathogenic mechanisms are largely unknown, S. flexneri employs its type III secretion system (T3SS) to hijack and disseminate throughout intestinal cells. Sun and colleagues use a multi-technique approach to demonstrate that one T3SS effector, IpaH4.5, is a GTPase-activating protein that disrupts transport of the mannose-6-phosphate receptor (CD-MPR) from Golgi to endosome. In doing so, S. flexneri disrupts MPR and lysosomal function, which is critical for its intracellular lifestyle, paracytophagy, and pathogenicity. Given rising concerns about antimicrobial resistance, these new insights may lead to new strategies for combating severe inflammation and epithelial destruction associated with this important pathogen.