Cellular Aspects of Shigella Pathogenesis: Focus on the Manipulation of Host Cell Processes

Abstract

Shigella is a Gram-negative bacterium that is responsible for shigellosis. Over the years, the study of Shigella has provided a greater understanding of how the host responds to bacterial infection, and how bacteria have evolved to effectively counter the host defenses. In this review, we provide an update on some of the most recent advances in our understanding of pivotal processes associated with Shigella infection, including the invasion into host cells, the metabolic changes that occur within the bacterium and the infected cell, cell-to-cell spread mechanisms, autophagy and membrane trafficking, inflammatory signaling and cell death. This recent progress sheds a new light into the mechanisms underlying Shigella pathogenesis, and also more generally provides deeper understanding of the complex interplay between host cells and bacterial pathogens in general.

Natural avirulentShigella boydiistrain in the Brazilian Amazon lacks major virulence genes and present Type II, Type III and Type VI Secretion Systems

“…Although this model lacks clinical relevance in context to the site of infection, in practice it’s a useful tool to measure immunization efficacy, protection against disease and determine the severity of infection (31). The lung model constitutes an organized mucosal lymphoid organ with T and B lymphocytes and antigen-presenting cells, when Shigella is inoculated intranasally occurs acute bronchopneumonia simulating shigellosis (32–38).…”

The species-spanning family of LPX-motif harbouring effector proteins

“…As a consequence, bacteria are released from dying macrophages and subsequently invade the surrounding epithelial cells from the basolateral surface by actively inducing cytoskeletal rearrangements. Soon after intracellular Shigella cells get surrounded by a vacuolar membrane, the bacteria manage to lyse this membrane and gain access to the cytosol, where they multiply and move intracellularly and intercellularly by exploiting the host cell actin machinery (for detailed reviews of Shigella pathogenesis, see,e.g., Killackey, Sorbara, & Girardin, ; Kuehl, Dragoi, Talman, & Agaisse, ).…”

“…Even though the biological relevance of SspH2 as a Salmonella effector protein eliciting an inflammatory response instead of mediating immune evasion is not yet clear and might appear counterintuitive at first glance, a concept termed "effector-triggered immune pathology" provides some plausible explanations (Stuart, Paquette, & Boyer, 2013 Soon after intracellular Shigella cells get surrounded by a vacuolar membrane, the bacteria manage to lyse this membrane and gain access to the cytosol, where they multiply and move intracellularly and intercellularly by exploiting the host cell actin machinery (for detailed reviews of Shigella pathogenesis, see,e.g., Killackey, Sorbara, & Girardin, 2016;Kuehl, Dragoi, Talman, & Agaisse, 2015). (Ashida, Toyotome, Nagai, & Sasakawa, 2007;Jin et al, 2002).…”

Using disruptive insertional mutagenesis to identify the in situ structure‐function landscape of the Shigella translocator protein IpaB

“…Because as few as 10–100 organisms can cause disease, regional epidemics are common in all parts of the world . Shigella uses its type III secretion system (T3SS) to translocate effector proteins into host cells to alter their normal functions for the benefit of the pathogen . Many important Gram‐negative pathogens use the T3SS as essential virulence factors and despite pathogen‐specific differences in T3SS effector functions, the T3SS apparatus (T3SA) maintains significant structural homology across diverse species boundaries .…”

“…4 Shigella uses its type III secretion system (T3SS) 1 to translocate effector proteins into host cells to alter their normal functions for the benefit of the pathogen. 5 Many important Gram-negative pathogens use the T3SS as essential virulence factors and despite pathogenspecific differences in T3SS effector functions, the T3SS apparatus (T3SA) maintains significant structural homology across diverse species boundaries. 6 The T3SA is anchored by a basal body that spans the entire bacterial envelope and supports an external needle composed of multiple copies of a small, polymerized needle protein terminating at a needle tip complex (TC) that maintains control of secretion.…”