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

Killackey SA, Sorbara MT, Girardin SE - Front Cell Infect Microbiol (2016)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto Toronto, ON, Canada.

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.

No MeSH data available.


Related in: MedlinePlus

Distinct phases of invasion and autophagy targeting during Shigella infection. Shigella adheres to the basolateral surface of epithelial cells, forms a pore in the eukaryotic membrane, and delivers effector proteins to induce its uptake (Box 1). The first wave of autophagy targeting follows initial invasion and is mediated by recruitment of the autophagy machinery to the site of entry. The intracellular PRRs, NOD1 and NOD2, play a critical role through the recruitment of ATG16L1. Following escape from the entry vacuole, Shigella drive actin polymerization at one pole through IcsA-dependent recruitment of N-WASP and ARP2/3. This allows for intracellular motility. This process is countered by the host's attempt to trap bacteria in septin-derived cages that enables autophagy targeting. Once motile and free in the cytosol the host is unable to target Shigella to autophagy. Actin-based motility allows Shigella to spread from cell-cell, and it efficiently escapes into the second cell using a reactivated T3SS. This secondary invasion event allows for additional autophagy targeting. IcsB mutants that are less efficient at escape are more readily targeted by autophagy at this step.
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Figure 1: Distinct phases of invasion and autophagy targeting during Shigella infection. Shigella adheres to the basolateral surface of epithelial cells, forms a pore in the eukaryotic membrane, and delivers effector proteins to induce its uptake (Box 1). The first wave of autophagy targeting follows initial invasion and is mediated by recruitment of the autophagy machinery to the site of entry. The intracellular PRRs, NOD1 and NOD2, play a critical role through the recruitment of ATG16L1. Following escape from the entry vacuole, Shigella drive actin polymerization at one pole through IcsA-dependent recruitment of N-WASP and ARP2/3. This allows for intracellular motility. This process is countered by the host's attempt to trap bacteria in septin-derived cages that enables autophagy targeting. Once motile and free in the cytosol the host is unable to target Shigella to autophagy. Actin-based motility allows Shigella to spread from cell-cell, and it efficiently escapes into the second cell using a reactivated T3SS. This secondary invasion event allows for additional autophagy targeting. IcsB mutants that are less efficient at escape are more readily targeted by autophagy at this step.

Mentions: Shigella triggers its own uptake into epithelial cells using a type III secretion system (T3SS) (Figure 1). The proteins of the T3SS are encoded by a large 220 kb virulence plasmid and form a macromolecular needle-like structure that allows for the delivery of effector proteins across the membrane of the target eukaryotic cell. Prior to delivery of effectors, Shigella first adheres to the host cell, despite the absence of classical adhesion proteins. Recent work has demonstrated that the Shigella surface protein, IcsA, functions as an adhesin that is activated by bile-salts, and facilitates interaction with host cells after initial activation of the T3SS (Brotcke Zumsteg et al., 2014). Bile-salts also promote the secretion of OspE1 and OspE2 which remain on the bacterial outer-membrane and increase adherence to polarized cells (Faherty et al., 2012). In addition, bile-salts, in particular deoxycholate, promote final assembly of the T3SS in an activation-ready state (Stensrud et al., 2008). Furthermore, bacterial binding to filopodia through the T3SS components, IpaB and IpaD, also promotes interaction and invasion (Romero et al., 2011). Interestingly, Marteyn et al. demonstrated that Shigella blocks secretion through the T3SS in anaerobic conditions through fumarate and nitrate reductase (FNR)-mediated suppression of spa32 and spa33 transcription (Marteyn et al., 2010). Detection of O2 in the region immediately adjacent to the epithelial barrier relieves this transcriptional suppression, triggering spa32 and spa33 expression leading to activation of the T3SS and efficient invasion (Marteyn et al., 2010). Altogether, these findings indicate that Shigella has evolved to acutely sense when it is in the appropriate gut environment to trigger increased adherence and T3SS activity.


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

Killackey SA, Sorbara MT, Girardin SE - Front Cell Infect Microbiol (2016)

Distinct phases of invasion and autophagy targeting during Shigella infection. Shigella adheres to the basolateral surface of epithelial cells, forms a pore in the eukaryotic membrane, and delivers effector proteins to induce its uptake (Box 1). The first wave of autophagy targeting follows initial invasion and is mediated by recruitment of the autophagy machinery to the site of entry. The intracellular PRRs, NOD1 and NOD2, play a critical role through the recruitment of ATG16L1. Following escape from the entry vacuole, Shigella drive actin polymerization at one pole through IcsA-dependent recruitment of N-WASP and ARP2/3. This allows for intracellular motility. This process is countered by the host's attempt to trap bacteria in septin-derived cages that enables autophagy targeting. Once motile and free in the cytosol the host is unable to target Shigella to autophagy. Actin-based motility allows Shigella to spread from cell-cell, and it efficiently escapes into the second cell using a reactivated T3SS. This secondary invasion event allows for additional autophagy targeting. IcsB mutants that are less efficient at escape are more readily targeted by autophagy at this step.
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Figure 1: Distinct phases of invasion and autophagy targeting during Shigella infection. Shigella adheres to the basolateral surface of epithelial cells, forms a pore in the eukaryotic membrane, and delivers effector proteins to induce its uptake (Box 1). The first wave of autophagy targeting follows initial invasion and is mediated by recruitment of the autophagy machinery to the site of entry. The intracellular PRRs, NOD1 and NOD2, play a critical role through the recruitment of ATG16L1. Following escape from the entry vacuole, Shigella drive actin polymerization at one pole through IcsA-dependent recruitment of N-WASP and ARP2/3. This allows for intracellular motility. This process is countered by the host's attempt to trap bacteria in septin-derived cages that enables autophagy targeting. Once motile and free in the cytosol the host is unable to target Shigella to autophagy. Actin-based motility allows Shigella to spread from cell-cell, and it efficiently escapes into the second cell using a reactivated T3SS. This secondary invasion event allows for additional autophagy targeting. IcsB mutants that are less efficient at escape are more readily targeted by autophagy at this step.
Mentions: Shigella triggers its own uptake into epithelial cells using a type III secretion system (T3SS) (Figure 1). The proteins of the T3SS are encoded by a large 220 kb virulence plasmid and form a macromolecular needle-like structure that allows for the delivery of effector proteins across the membrane of the target eukaryotic cell. Prior to delivery of effectors, Shigella first adheres to the host cell, despite the absence of classical adhesion proteins. Recent work has demonstrated that the Shigella surface protein, IcsA, functions as an adhesin that is activated by bile-salts, and facilitates interaction with host cells after initial activation of the T3SS (Brotcke Zumsteg et al., 2014). Bile-salts also promote the secretion of OspE1 and OspE2 which remain on the bacterial outer-membrane and increase adherence to polarized cells (Faherty et al., 2012). In addition, bile-salts, in particular deoxycholate, promote final assembly of the T3SS in an activation-ready state (Stensrud et al., 2008). Furthermore, bacterial binding to filopodia through the T3SS components, IpaB and IpaD, also promotes interaction and invasion (Romero et al., 2011). Interestingly, Marteyn et al. demonstrated that Shigella blocks secretion through the T3SS in anaerobic conditions through fumarate and nitrate reductase (FNR)-mediated suppression of spa32 and spa33 transcription (Marteyn et al., 2010). Detection of O2 in the region immediately adjacent to the epithelial barrier relieves this transcriptional suppression, triggering spa32 and spa33 expression leading to activation of the T3SS and efficient invasion (Marteyn et al., 2010). Altogether, these findings indicate that Shigella has evolved to acutely sense when it is in the appropriate gut environment to trigger increased adherence and T3SS activity.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto Toronto, ON, Canada.

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.

No MeSH data available.


Related in: MedlinePlus