The <named-content content-type="genus-species">Listeria monocytogenes</named-content> ChiA Chitinase Enhances Virulence through Suppression of Host Innate Immunity

ABSTRACT Environmental pathogens survive and replicate within the outside environment while maintaining the capacity to infect mammalian hosts. For some microorganisms, mammalian infection may be a relatively rare event. Understanding how environmental pathogens retain their ability to cause disease...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Swarnava Chaudhuri, Benjamin N. Gantner, Richard D. Ye, Nicholas P. Cianciotto, Nancy E. Freitag
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2013
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/6f3df39f694e4ad1b08be711e308672c
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:6f3df39f694e4ad1b08be711e308672c
record_format	dspace
spelling	oai:doaj.org-article:6f3df39f694e4ad1b08be711e308672c2021-11-15T15:40:26ZThe <named-content content-type="genus-species">Listeria monocytogenes</named-content> ChiA Chitinase Enhances Virulence through Suppression of Host Innate Immunity10.1128/mBio.00617-122150-7511https://doaj.org/article/6f3df39f694e4ad1b08be711e308672c2013-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00617-12https://doaj.org/toc/2150-7511ABSTRACT Environmental pathogens survive and replicate within the outside environment while maintaining the capacity to infect mammalian hosts. For some microorganisms, mammalian infection may be a relatively rare event. Understanding how environmental pathogens retain their ability to cause disease may provide insight into environmental reservoirs of disease and emerging infections. Listeria monocytogenes survives as a saprophyte in soil but is capable of causing serious invasive disease in susceptible individuals. The bacterium secretes virulence factors that promote cell invasion, bacterial replication, and cell-to-cell spread. Recently, an L. monocytogenes chitinase (ChiA) was shown to enhance bacterial infection in mice. Given that mammals do not synthesize chitin, the function of ChiA within infected animals was not clear. Here we have demonstrated that ChiA enhances L. monocytogenes survival in vivo through the suppression of host innate immunity. L. monocytogenes ΔchiA mutants were fully capable of establishing bacterial replication within target organs during the first 48 h of infection. By 72 to 96 h postinfection, however, numbers of ΔchiA bacteria diminished, indicative of an effective immune response to contain infection. The ΔchiA-associated virulence defect could be complemented in trans by wild-type L. monocytogenes, suggesting that secreted ChiA altered a target that resulted in a more permissive host environment for bacterial replication. ChiA secretion resulted in a dramatic decrease in inducible nitric oxide synthase (iNOS) expression, and ΔchiA mutant virulence was restored in NOS2−/− mice lacking iNOS. This work is the first to demonstrate modulation of a specific host innate immune response by a bacterial chitinase. IMPORTANCE Bacterial chitinases have traditionally been viewed as enzymes that either hydrolyze chitin as a food source or serve as a defense mechanism against organisms containing structural chitin (such as fungi). Recent evidence indicates that bacterial chitinases and chitin-binding proteins contribute to pathogenesis, primarily via bacterial adherence to chitin-like molecules present on the surface of mammalian cells. In contrast, mammalian chitinases have been linked to immunity via inflammatory immune responses that occur outside the context of infection, and since mammals do not produce chitin, the targets of these mammalian chitinases have remained elusive. This work demonstrates that a Listeria monocytogenes-secreted chitinase has distinct functional roles that include chitin hydrolysis and suppression of host innate immunity. The established link between chitinase and the inhibition of host inducible nitric oxide synthase (iNOS) expression may help clarify the thus far elusive relationship observed between mammalian chitinase enzymes and host inflammatory responses occurring in the absence of infection.Swarnava ChaudhuriBenjamin N. GantnerRichard D. YeNicholas P. CianciottoNancy E. FreitagAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 4, Iss 2 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Swarnava Chaudhuri Benjamin N. Gantner Richard D. Ye Nicholas P. Cianciotto Nancy E. Freitag The <named-content content-type="genus-species">Listeria monocytogenes</named-content> ChiA Chitinase Enhances Virulence through Suppression of Host Innate Immunity
description	ABSTRACT Environmental pathogens survive and replicate within the outside environment while maintaining the capacity to infect mammalian hosts. For some microorganisms, mammalian infection may be a relatively rare event. Understanding how environmental pathogens retain their ability to cause disease may provide insight into environmental reservoirs of disease and emerging infections. Listeria monocytogenes survives as a saprophyte in soil but is capable of causing serious invasive disease in susceptible individuals. The bacterium secretes virulence factors that promote cell invasion, bacterial replication, and cell-to-cell spread. Recently, an L. monocytogenes chitinase (ChiA) was shown to enhance bacterial infection in mice. Given that mammals do not synthesize chitin, the function of ChiA within infected animals was not clear. Here we have demonstrated that ChiA enhances L. monocytogenes survival in vivo through the suppression of host innate immunity. L. monocytogenes ΔchiA mutants were fully capable of establishing bacterial replication within target organs during the first 48 h of infection. By 72 to 96 h postinfection, however, numbers of ΔchiA bacteria diminished, indicative of an effective immune response to contain infection. The ΔchiA-associated virulence defect could be complemented in trans by wild-type L. monocytogenes, suggesting that secreted ChiA altered a target that resulted in a more permissive host environment for bacterial replication. ChiA secretion resulted in a dramatic decrease in inducible nitric oxide synthase (iNOS) expression, and ΔchiA mutant virulence was restored in NOS2−/− mice lacking iNOS. This work is the first to demonstrate modulation of a specific host innate immune response by a bacterial chitinase. IMPORTANCE Bacterial chitinases have traditionally been viewed as enzymes that either hydrolyze chitin as a food source or serve as a defense mechanism against organisms containing structural chitin (such as fungi). Recent evidence indicates that bacterial chitinases and chitin-binding proteins contribute to pathogenesis, primarily via bacterial adherence to chitin-like molecules present on the surface of mammalian cells. In contrast, mammalian chitinases have been linked to immunity via inflammatory immune responses that occur outside the context of infection, and since mammals do not produce chitin, the targets of these mammalian chitinases have remained elusive. This work demonstrates that a Listeria monocytogenes-secreted chitinase has distinct functional roles that include chitin hydrolysis and suppression of host innate immunity. The established link between chitinase and the inhibition of host inducible nitric oxide synthase (iNOS) expression may help clarify the thus far elusive relationship observed between mammalian chitinase enzymes and host inflammatory responses occurring in the absence of infection.
format	article
author	Swarnava Chaudhuri Benjamin N. Gantner Richard D. Ye Nicholas P. Cianciotto Nancy E. Freitag
author_facet	Swarnava Chaudhuri Benjamin N. Gantner Richard D. Ye Nicholas P. Cianciotto Nancy E. Freitag
author_sort	Swarnava Chaudhuri
title	The <named-content content-type="genus-species">Listeria monocytogenes</named-content> ChiA Chitinase Enhances Virulence through Suppression of Host Innate Immunity
title_short	The <named-content content-type="genus-species">Listeria monocytogenes</named-content> ChiA Chitinase Enhances Virulence through Suppression of Host Innate Immunity
title_full	The <named-content content-type="genus-species">Listeria monocytogenes</named-content> ChiA Chitinase Enhances Virulence through Suppression of Host Innate Immunity
title_fullStr	The <named-content content-type="genus-species">Listeria monocytogenes</named-content> ChiA Chitinase Enhances Virulence through Suppression of Host Innate Immunity
title_full_unstemmed	The <named-content content-type="genus-species">Listeria monocytogenes</named-content> ChiA Chitinase Enhances Virulence through Suppression of Host Innate Immunity
title_sort	<named-content content-type="genus-species">listeria monocytogenes</named-content> chia chitinase enhances virulence through suppression of host innate immunity
publisher	American Society for Microbiology
publishDate	2013
url	https://doaj.org/article/6f3df39f694e4ad1b08be711e308672c
work_keys_str_mv	AT swarnavachaudhuri thenamedcontentcontenttypegenusspecieslisteriamonocytogenesnamedcontentchiachitinaseenhancesvirulencethroughsuppressionofhostinnateimmunity AT benjaminngantner thenamedcontentcontenttypegenusspecieslisteriamonocytogenesnamedcontentchiachitinaseenhancesvirulencethroughsuppressionofhostinnateimmunity AT richarddye thenamedcontentcontenttypegenusspecieslisteriamonocytogenesnamedcontentchiachitinaseenhancesvirulencethroughsuppressionofhostinnateimmunity AT nicholaspcianciotto thenamedcontentcontenttypegenusspecieslisteriamonocytogenesnamedcontentchiachitinaseenhancesvirulencethroughsuppressionofhostinnateimmunity AT nancyefreitag thenamedcontentcontenttypegenusspecieslisteriamonocytogenesnamedcontentchiachitinaseenhancesvirulencethroughsuppressionofhostinnateimmunity AT swarnavachaudhuri namedcontentcontenttypegenusspecieslisteriamonocytogenesnamedcontentchiachitinaseenhancesvirulencethroughsuppressionofhostinnateimmunity AT benjaminngantner namedcontentcontenttypegenusspecieslisteriamonocytogenesnamedcontentchiachitinaseenhancesvirulencethroughsuppressionofhostinnateimmunity AT richarddye namedcontentcontenttypegenusspecieslisteriamonocytogenesnamedcontentchiachitinaseenhancesvirulencethroughsuppressionofhostinnateimmunity AT nicholaspcianciotto namedcontentcontenttypegenusspecieslisteriamonocytogenesnamedcontentchiachitinaseenhancesvirulencethroughsuppressionofhostinnateimmunity AT nancyefreitag namedcontentcontenttypegenusspecieslisteriamonocytogenesnamedcontentchiachitinaseenhancesvirulencethroughsuppressionofhostinnateimmunity
_version_	1718427770440122368

The <named-content content-type="genus-species">Listeria monocytogenes</named-content> ChiA Chitinase Enhances Virulence through Suppression of Host Innate Immunity

Ejemplares similares