Manipulation of epithelial cell death pathways by Shigella

Abstract

Shigella, a major cause of bacterial dysentery, knows when it is not wanted. To generate and maintain its niche within host cells, this unwelcome guest injects several dozen virulence factors via a type 3 secretion system (T3SS). In this issue, Ashida et al (2020) have elucidated the role of two such factors from Shigella flexneri-OspC1 and OspD3-that together counteract apoptotic and necroptotic death pathways in colonised epithelial cells. As a result, Shigella can replicate to high levels within the colonic epithelium, leading to the substantial epithelial damage in shigellosis and efficient bacterial release for faecal transmission.

Figure 1. Shigella fights to maintain its replicative niche within epithelial cells by delivering T3SS effectors to inhibit three major programmed cell death pathways

Early in the infection, OspC3 prevents caspase‐4‐dependent pyroptosis. In the later stages of infection, apoptosis is activated through an unknown mechanism, and OspC1 counters this, by preventing caspase‐8 activation. The host cell recognises this inhibition of caspase‐8 and triggers necroptosis as a backup death pathway, through RIPK1 and RIPK3 interaction and subsequent phosphorylation and activation of MLKL. The third effector, OspD3, blocks this pathway by cleaving RIPK1 and RIPK3, which targets them for degradation.