Molecular Pathogenesis ofShigellaspp.: Controlling Host Cell Signaling, Invasion, and Death by Type III Secretion

Abstract

SUMMARY Shigella spp. are gram-negative pathogenic bacteria that evolved from harmless enterobacterial relatives and may cause devastating diarrhea upon ingestion. Research performed over the last 25 years revealed that a type III secretion system (T3SS) encoded on a large plasmid is a key virulence factor of Shigella flexneri. The T3SS determines the interactions of S. flexneri with intestinal cells by consecutively translocating two sets of effector proteins into the target cells. Thus, S. flexneri controls invasion into EC, intra- and intercellular spread, macrophage cell death, as well as host inflammatory responses. Some of the translocated effector proteins show novel biochemical activities by which they intercept host cell signal transduction pathways. An understanding of the molecular mechanisms underlying Shigella pathogenesis will foster the development of a safe and efficient vaccine, which, in parallel with improved hygiene, should curb infections by this widespread pathogen.

Oligomeric states of the Shigella translocator protein IpaB provide structural insights into formation of the type III secretion translocon

“…The T3SS is an essential virulence system that translocates bacterial effector proteins into host cells to alter normal cell functions for the benefit of the pathogen. 3,4 Many important pathogens employ T3SSs as virulence mechanisms and while there are distinct pathogen-specific differences in T3SS effector functions, the Type III secretion apparatus (T3SA) maintains significant structural homology across diverse species boundaries. 3 In all cases, the T3SA is anchored in the bacterial envelope by a basal body, which supports an external needle composed of many copies of a small, polymerized needle protein terminating at a needle tip complex that contributes to secretion control.…”

“…3,4 Many important pathogens employ T3SSs as virulence mechanisms and while there are distinct pathogen-specific differences in T3SS effector functions, the Type III secretion apparatus (T3SA) maintains significant structural homology across diverse species boundaries. 3 In all cases, the T3SA is anchored in the bacterial envelope by a basal body, which supports an external needle composed of many copies of a small, polymerized needle protein terminating at a needle tip complex that contributes to secretion control. 5 Shigella is currently the only pathogen for which each step in the T3SA needle tip complex maturation can be artificially induced to mimic natural maturation.…”

Towards a non-living vaccine against Shigella flexneri: From the inactivation procedure to protection studies

“…Among them, shigellosis is one of the most contagious types of diarrhea caused by bacteria. Shigella spp, the causative agent, invades the intestinal mucosa, spreads to the adjacent epithelial cells and causes tissue damage, fluid secretion and inflammation, producing the clinical manifestations of dysentery, diarrhea with blood and mucus [2]. Shigellosis is endemic throughout the world where it is responsible for more than 165 million cases of severe dysentery annually, the majority of which occur in children under 5 years old in the developing world [3].…”

Natural products modulate Shigella–host-cell interaction

“…Shigella and enteroinvasive Escherichia coli form a pathovar sharing similar virulence properties (Schroeder & Hilbi, 2008). These micro-organisms, which rely on the type 3 secretion system, are able to invade many types of cell, including epithelial cells and macrophages, by injecting effector proteins into the host cell.…”