Abstract

Shigella comprises four species of human-restricted pathogens causing bacillary dysentery. While Shigella possesses multiple genetic loci contributing to virulence, a type III secretion system (T3SS) is its primary virulence factor. The Shigella T3SS nanomachine consists of four major assemblies: the cytoplasmic sorting platform; the envelope-spanning core/basal body; an exposed needle; and a needle-associated tip complex with associated translocon that is inserted into host cell membranes. The initial subversion of host cell activities is carried out by the effector functions of the invasion plasmid antigen (Ipa) translocator proteins, with the cell ultimately being controlled by dedicated effector proteins that are injected into the host cytoplasm though the translocon. Much of the information now available on the T3SS injectisome has been accumulated through collective studies on the T3SS from three systems, those of Shigella flexneri, Salmonella typhimurium and Yersinia enterocolitica/Yersinia pestis. In this review, we will touch upon the important features of the T3SS injectisome that have come to light because of research in the Shigella and closely related systems. We will also briefly highlight some of the strategies being considered to target the Shigella T3SS for disease prevention.

Highlights

  • Much of the detailed information that is available on the T3SS injectisome has been generated through detailed studies on the T3SS injectisome of species belonging to three bacterial genera—Shigella flexneri, Salmonella typhimurium and Yersinia enterocolitica/Yersinia pestis

  • The Shigella injectisome needle has an outside diameter of about 7 nm and an inner channel diameter of 2.5 nm with the MxiH monomers assembled in a helical manner with ~5.6 subunits per turn [49]

  • It should be noted that some groups suggest that IpaB may be a component of the tip complex [32,34,67,69] and this is how it contributes to the control of type III secretion in Shigella

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Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Many important Gram-negative bacterial pathogens of plants and animals use type III secretion systems (T3SS) to initiate contact with target eukaryotic cells to manipulate those cells for the benefit of the pathogen [1]. While largely restricted to communication with eukaryotic targets, T3SSs have a strong evolutionary relationship with the Gram-negative flagellum [2], which at its core uses the flagellar-T3SS (fT3SS) as a secretion apparatus, in part to assemble the extracellular flagellar components. The virulence T3SS apparatus or injectisome is architecturally well conserved with regard to its cytoplasmic, core and extracellular assemblies [3,4,5,6,7]. This review will focus on some of the facets of the Shigella T3SS and injectisome. Included will be a discussion of how the Shigella system has improved our overall understanding of these systems and how it may be targeted for improving public health

A Brief Overview of Shigella
The Needle
Model of tip theprotein tip protein complex the injectisome
Tip Complex Maturation
Completion of the Translocon and Induction of Secretion
The Major Ring Components of the Basal Body
The Accessory Components of the Injectisome Basal Body
The Sorting Platform Components
The first reported the in situ
Functional Features of the Sorting Platform
Targeting the Shigella T3SS with Small Molecule Anti-Infective Agents
Prophylactic Shigella Vaccines Targeting the Injectisome
Findings
Looking to the Future
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