The orchestrators of Shigella flexneri infection

Abstract

Shigella flexneri is a pathogenic bacterium with an intriguing set of effectors which collectively orchestrate a truly successful mode of infection. The main effector contributing to the process of entry is IpgB1 associated with Spa15, a type three secretion (TTS) chaperone. Once secreted, IpgB1 skilfully hijacks the RhoG-ELMO-Dock180 pathway to stimulate membrane ruffling resulting in S. flexneri entry into the host. Escape from autophagy is the role of the IcsB effector which is associated with another TTS chaperone, IpgA. The secreted IcsB is able to mask VirG from detection by the autophagy protein and prevents destruction of the bacterium upon entry. Colonization of the host cell is mainly down to a late secreted effector, IpaH9.8, which enters the nucleus and inhibits the role of U2AF35 in splicing activity. IpaH9.8 C-terminal domain which has structural flexibility and ubiquitin ligase activity binds to U2AF35 and down-regulates pro-inflammatory responses by the host cell, allowing S. flexneri to colonize. Intracellular and intercellular movements of S. flexneri and thus the ability for the bacterium to spread to neighbouring cells is orchestrated by the surface-exposed protein VirG which interacts with vinculin and N-WASP and promotes actin polymerization.