<italic toggle="yes">Shigella sonnei</italic> O-Antigen Inhibits Internalization, Vacuole Escape, and Inflammasome Activation

ABSTRACT Two Shigella species, Shigella flexneri and Shigella sonnei, cause approximately 90% of bacterial dysentery worldwide. While S. flexneri is the dominant species in low-income countries, S. sonnei causes the majority of infections in middle- and high-income countries. S. flexneri is a protot...

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Autores principales:	Jayne L. Watson, Julia Sanchez-Garrido, Philippa J. Goddard, Vincenzo Torraca, Serge Mostowy, Avinash R. Shenoy, Abigail Clements
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	O-Antigen Shigella host-pathogen interactions inflammasomes macrophages Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/499a8957663b4f078a3605eeebf1ef45
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spelling	oai:doaj.org-article:499a8957663b4f078a3605eeebf1ef452021-11-15T15:54:45Z<italic toggle="yes">Shigella sonnei</italic> O-Antigen Inhibits Internalization, Vacuole Escape, and Inflammasome Activation10.1128/mBio.02654-192150-7511https://doaj.org/article/499a8957663b4f078a3605eeebf1ef452019-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02654-19https://doaj.org/toc/2150-7511ABSTRACT Two Shigella species, Shigella flexneri and Shigella sonnei, cause approximately 90% of bacterial dysentery worldwide. While S. flexneri is the dominant species in low-income countries, S. sonnei causes the majority of infections in middle- and high-income countries. S. flexneri is a prototypic cytosolic bacterium; once intracellular, it rapidly escapes the phagocytic vacuole and causes pyroptosis of macrophages, which is important for pathogenesis and bacterial spread. In contrast, little is known about the invasion, vacuole escape, and induction of pyroptosis during S. sonnei infection of macrophages. We demonstrate here that S. sonnei causes substantially less pyroptosis in human primary monocyte-derived macrophages and THP1 cells. This is due to reduced bacterial uptake and lower relative vacuole escape, which results in fewer cytosolic S. sonnei and hence reduced activation of caspase-1 inflammasomes. Mechanistically, the O-antigen (O-Ag), which in S. sonnei is contained in both the lipopolysaccharide and the capsule, was responsible for reduced uptake and the type 3 secretion system (T3SS) was required for vacuole escape. Our findings suggest that S. sonnei has adapted to an extracellular lifestyle by incorporating multiple layers of O-Ag onto its surface compared to other Shigella species. IMPORTANCE Diarrheal disease remains the second leading cause of death in children under five. Shigella remains a significant cause of diarrheal disease with two species, S. flexneri and S. sonnei, causing the majority of infections. S. flexneri are well known to cause cell death in macrophages, which contributes to the inflammatory nature of Shigella diarrhea. Here, we demonstrate that S. sonnei causes less cell death than S. flexneri due to a reduced number of bacteria present in the cell cytosol. We identify the O-Ag polysaccharide which, uniquely among Shigella spp., is present in two forms on the bacterial cell surface as the bacterial factor responsible. Our data indicate that S. sonnei differs from S. flexneri in key aspects of infection and that more attention should be given to characterization of S. sonnei infection.Jayne L. WatsonJulia Sanchez-GarridoPhilippa J. GoddardVincenzo TorracaSerge MostowyAvinash R. ShenoyAbigail ClementsAmerican Society for MicrobiologyarticleO-AntigenShigellahost-pathogen interactionsinflammasomesmacrophagesMicrobiologyQR1-502ENmBio, Vol 10, Iss 6 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	O-Antigen Shigella host-pathogen interactions inflammasomes macrophages Microbiology QR1-502
spellingShingle	O-Antigen Shigella host-pathogen interactions inflammasomes macrophages Microbiology QR1-502 Jayne L. Watson Julia Sanchez-Garrido Philippa J. Goddard Vincenzo Torraca Serge Mostowy Avinash R. Shenoy Abigail Clements <italic toggle="yes">Shigella sonnei</italic> O-Antigen Inhibits Internalization, Vacuole Escape, and Inflammasome Activation
description	ABSTRACT Two Shigella species, Shigella flexneri and Shigella sonnei, cause approximately 90% of bacterial dysentery worldwide. While S. flexneri is the dominant species in low-income countries, S. sonnei causes the majority of infections in middle- and high-income countries. S. flexneri is a prototypic cytosolic bacterium; once intracellular, it rapidly escapes the phagocytic vacuole and causes pyroptosis of macrophages, which is important for pathogenesis and bacterial spread. In contrast, little is known about the invasion, vacuole escape, and induction of pyroptosis during S. sonnei infection of macrophages. We demonstrate here that S. sonnei causes substantially less pyroptosis in human primary monocyte-derived macrophages and THP1 cells. This is due to reduced bacterial uptake and lower relative vacuole escape, which results in fewer cytosolic S. sonnei and hence reduced activation of caspase-1 inflammasomes. Mechanistically, the O-antigen (O-Ag), which in S. sonnei is contained in both the lipopolysaccharide and the capsule, was responsible for reduced uptake and the type 3 secretion system (T3SS) was required for vacuole escape. Our findings suggest that S. sonnei has adapted to an extracellular lifestyle by incorporating multiple layers of O-Ag onto its surface compared to other Shigella species. IMPORTANCE Diarrheal disease remains the second leading cause of death in children under five. Shigella remains a significant cause of diarrheal disease with two species, S. flexneri and S. sonnei, causing the majority of infections. S. flexneri are well known to cause cell death in macrophages, which contributes to the inflammatory nature of Shigella diarrhea. Here, we demonstrate that S. sonnei causes less cell death than S. flexneri due to a reduced number of bacteria present in the cell cytosol. We identify the O-Ag polysaccharide which, uniquely among Shigella spp., is present in two forms on the bacterial cell surface as the bacterial factor responsible. Our data indicate that S. sonnei differs from S. flexneri in key aspects of infection and that more attention should be given to characterization of S. sonnei infection.
format	article
author	Jayne L. Watson Julia Sanchez-Garrido Philippa J. Goddard Vincenzo Torraca Serge Mostowy Avinash R. Shenoy Abigail Clements
author_facet	Jayne L. Watson Julia Sanchez-Garrido Philippa J. Goddard Vincenzo Torraca Serge Mostowy Avinash R. Shenoy Abigail Clements
author_sort	Jayne L. Watson
title	<italic toggle="yes">Shigella sonnei</italic> O-Antigen Inhibits Internalization, Vacuole Escape, and Inflammasome Activation
title_short	<italic toggle="yes">Shigella sonnei</italic> O-Antigen Inhibits Internalization, Vacuole Escape, and Inflammasome Activation
title_full	<italic toggle="yes">Shigella sonnei</italic> O-Antigen Inhibits Internalization, Vacuole Escape, and Inflammasome Activation
title_fullStr	<italic toggle="yes">Shigella sonnei</italic> O-Antigen Inhibits Internalization, Vacuole Escape, and Inflammasome Activation
title_full_unstemmed	<italic toggle="yes">Shigella sonnei</italic> O-Antigen Inhibits Internalization, Vacuole Escape, and Inflammasome Activation
title_sort	<italic toggle="yes">shigella sonnei</italic> o-antigen inhibits internalization, vacuole escape, and inflammasome activation
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/499a8957663b4f078a3605eeebf1ef45
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<italic toggle="yes">Shigella sonnei</italic> O-Antigen Inhibits Internalization, Vacuole Escape, and Inflammasome Activation

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