Ubiquitination of <italic toggle="yes">Listeria</italic> Virulence Factor InlC Contributes to the Host Response to Infection

ABSTRACT Listeria monocytogenes is a pathogenic bacterium causing potentially fatal foodborne infections in humans and animals. While the mechanisms used by Listeria to manipulate its host have been thoroughly characterized, how the host controls bacterial virulence factors remains to be extensively...

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Autores principales:	Edith Gouin, Damien Balestrino, Orhan Rasid, Marie-Anne Nahori, Véronique Villiers, Francis Impens, Stevenn Volant, Thomas Vogl, Yves Jacob, Olivier Dussurget, Pascale Cossart
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Listeria monocytogenes ubiquitination pathogenesis alarmin inflammation Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/581f08c8189d4367abe55222fb84327f
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spelling	oai:doaj.org-article:581f08c8189d4367abe55222fb84327f2021-11-15T15:54:45ZUbiquitination of <italic toggle="yes">Listeria</italic> Virulence Factor InlC Contributes to the Host Response to Infection10.1128/mBio.02778-192150-7511https://doaj.org/article/581f08c8189d4367abe55222fb84327f2019-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02778-19https://doaj.org/toc/2150-7511ABSTRACT Listeria monocytogenes is a pathogenic bacterium causing potentially fatal foodborne infections in humans and animals. While the mechanisms used by Listeria to manipulate its host have been thoroughly characterized, how the host controls bacterial virulence factors remains to be extensively deciphered. Here, we found that the secreted Listeria virulence protein InlC is monoubiquitinated by the host cell machinery on K224, restricting infection. We show that the ubiquitinated form of InlC interacts with the intracellular alarmin S100A9, resulting in its stabilization and in increased reactive oxygen species production by neutrophils in infected mice. Collectively, our results suggest that posttranslational modification of InlC exacerbates the host response upon Listeria infection. IMPORTANCE The pathogenic potential of Listeria monocytogenes relies on the production of an arsenal of virulence determinants that have been extensively characterized, including surface and secreted proteins of the internalin family. We have previously shown that the Listeria secreted internalin InlC interacts with IκB kinase α to interfere with the host immune response (E. Gouin, M. Adib-Conquy, D. Balestrino, M.-A. Nahori, et al., Proc Natl Acad Sci USA, 107:17333–17338, 2010, https://doi.org/10.1073/pnas.1007765107). In the present work, we report that InlC is monoubiquitinated on K224 upon infection of cells and provide evidence that ubiquitinated InlC interacts with and stabilizes the alarmin S100A9, which is a critical regulator of the immune response and inflammatory processes. Additionally, we show that ubiquitination of InlC causes an increase in reactive oxygen species production by neutrophils in mice and restricts Listeria infection. These findings are the first to identify a posttranscriptional modification of an internalin contributing to host defense.Edith GouinDamien BalestrinoOrhan RasidMarie-Anne NahoriVéronique VilliersFrancis ImpensStevenn VolantThomas VoglYves JacobOlivier DussurgetPascale CossartAmerican Society for MicrobiologyarticleListeria monocytogenesubiquitinationpathogenesisalarmininflammationMicrobiologyQR1-502ENmBio, Vol 10, Iss 6 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Listeria monocytogenes ubiquitination pathogenesis alarmin inflammation Microbiology QR1-502
spellingShingle	Listeria monocytogenes ubiquitination pathogenesis alarmin inflammation Microbiology QR1-502 Edith Gouin Damien Balestrino Orhan Rasid Marie-Anne Nahori Véronique Villiers Francis Impens Stevenn Volant Thomas Vogl Yves Jacob Olivier Dussurget Pascale Cossart Ubiquitination of <italic toggle="yes">Listeria</italic> Virulence Factor InlC Contributes to the Host Response to Infection
description	ABSTRACT Listeria monocytogenes is a pathogenic bacterium causing potentially fatal foodborne infections in humans and animals. While the mechanisms used by Listeria to manipulate its host have been thoroughly characterized, how the host controls bacterial virulence factors remains to be extensively deciphered. Here, we found that the secreted Listeria virulence protein InlC is monoubiquitinated by the host cell machinery on K224, restricting infection. We show that the ubiquitinated form of InlC interacts with the intracellular alarmin S100A9, resulting in its stabilization and in increased reactive oxygen species production by neutrophils in infected mice. Collectively, our results suggest that posttranslational modification of InlC exacerbates the host response upon Listeria infection. IMPORTANCE The pathogenic potential of Listeria monocytogenes relies on the production of an arsenal of virulence determinants that have been extensively characterized, including surface and secreted proteins of the internalin family. We have previously shown that the Listeria secreted internalin InlC interacts with IκB kinase α to interfere with the host immune response (E. Gouin, M. Adib-Conquy, D. Balestrino, M.-A. Nahori, et al., Proc Natl Acad Sci USA, 107:17333–17338, 2010, https://doi.org/10.1073/pnas.1007765107). In the present work, we report that InlC is monoubiquitinated on K224 upon infection of cells and provide evidence that ubiquitinated InlC interacts with and stabilizes the alarmin S100A9, which is a critical regulator of the immune response and inflammatory processes. Additionally, we show that ubiquitination of InlC causes an increase in reactive oxygen species production by neutrophils in mice and restricts Listeria infection. These findings are the first to identify a posttranscriptional modification of an internalin contributing to host defense.
format	article
author	Edith Gouin Damien Balestrino Orhan Rasid Marie-Anne Nahori Véronique Villiers Francis Impens Stevenn Volant Thomas Vogl Yves Jacob Olivier Dussurget Pascale Cossart
author_facet	Edith Gouin Damien Balestrino Orhan Rasid Marie-Anne Nahori Véronique Villiers Francis Impens Stevenn Volant Thomas Vogl Yves Jacob Olivier Dussurget Pascale Cossart
author_sort	Edith Gouin
title	Ubiquitination of <italic toggle="yes">Listeria</italic> Virulence Factor InlC Contributes to the Host Response to Infection
title_short	Ubiquitination of <italic toggle="yes">Listeria</italic> Virulence Factor InlC Contributes to the Host Response to Infection
title_full	Ubiquitination of <italic toggle="yes">Listeria</italic> Virulence Factor InlC Contributes to the Host Response to Infection
title_fullStr	Ubiquitination of <italic toggle="yes">Listeria</italic> Virulence Factor InlC Contributes to the Host Response to Infection
title_full_unstemmed	Ubiquitination of <italic toggle="yes">Listeria</italic> Virulence Factor InlC Contributes to the Host Response to Infection
title_sort	ubiquitination of <italic toggle="yes">listeria</italic> virulence factor inlc contributes to the host response to infection
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/581f08c8189d4367abe55222fb84327f
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Ubiquitination of <italic toggle="yes">Listeria</italic> Virulence Factor InlC Contributes to the Host Response to Infection

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