Inhibition of calpain blocks the phagosomal escape of Listeria monocytogenes.

Listeria monocytogenes is a gram-positive facultative intracellular bacterium responsible for the food borne infection listeriosis, affecting principally the immunocompromised, the old, neonates and pregnant women. Following invasion L. monocytogenes escapes the phagosome and replicates in the cytop...

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Autores principales:	Gloria Lopez-Castejon, David Corbett, Marie Goldrick, Ian S Roberts, David Brough
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/aa3e2fd0d13a4f7eaa44d8a8a6f27ffe
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spelling	oai:doaj.org-article:aa3e2fd0d13a4f7eaa44d8a8a6f27ffe2021-11-25T06:23:49ZInhibition of calpain blocks the phagosomal escape of Listeria monocytogenes.1932-620310.1371/journal.pone.0035936https://doaj.org/article/aa3e2fd0d13a4f7eaa44d8a8a6f27ffe2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22563421/?tool=EBIhttps://doaj.org/toc/1932-6203Listeria monocytogenes is a gram-positive facultative intracellular bacterium responsible for the food borne infection listeriosis, affecting principally the immunocompromised, the old, neonates and pregnant women. Following invasion L. monocytogenes escapes the phagosome and replicates in the cytoplasm. Phagosome escape is central to L. monocytogenes virulence and is required for initiating innate host-defence responses such as the secretion of the cytokine interleukin-1. Phagosome escape of L. monocytogenes is reported to depend upon host proteins such as γ-interferon-inducible lysosomal thiol reductase and the cystic fibrosis transmembrane conductance regulator. The host cytosolic cysteine protease calpain is required in the life cycle of numerous pathogens, and previous research reports an activation of calpain by L. monocytogenes infection. Thus we sought to determine whether host calpain was required for the virulence of L. monocytogenes. Treatment of macrophages with calpain inhibitors blocked escape of L. monocytogenes from the phagosome and consequently its proliferation within the cytosol. This was independent of any direct effect on the production of bacterial virulence factors or of a bactericidal effect. Furthermore, the secretion of interleukin-1β, a host cytokine whose secretion induced by L. monocytogenes depends upon phagosome escape, was also blocked by calpain inhibition. These data indicate that L. monocytogenes co-opts host calpain to facilitate its escape from the phagosome, and more generally, that calpain may represent a cellular Achilles heel exploited by pathogens.Gloria Lopez-CastejonDavid CorbettMarie GoldrickIan S RobertsDavid BroughPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e35936 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Gloria Lopez-Castejon David Corbett Marie Goldrick Ian S Roberts David Brough Inhibition of calpain blocks the phagosomal escape of Listeria monocytogenes.
description	Listeria monocytogenes is a gram-positive facultative intracellular bacterium responsible for the food borne infection listeriosis, affecting principally the immunocompromised, the old, neonates and pregnant women. Following invasion L. monocytogenes escapes the phagosome and replicates in the cytoplasm. Phagosome escape is central to L. monocytogenes virulence and is required for initiating innate host-defence responses such as the secretion of the cytokine interleukin-1. Phagosome escape of L. monocytogenes is reported to depend upon host proteins such as γ-interferon-inducible lysosomal thiol reductase and the cystic fibrosis transmembrane conductance regulator. The host cytosolic cysteine protease calpain is required in the life cycle of numerous pathogens, and previous research reports an activation of calpain by L. monocytogenes infection. Thus we sought to determine whether host calpain was required for the virulence of L. monocytogenes. Treatment of macrophages with calpain inhibitors blocked escape of L. monocytogenes from the phagosome and consequently its proliferation within the cytosol. This was independent of any direct effect on the production of bacterial virulence factors or of a bactericidal effect. Furthermore, the secretion of interleukin-1β, a host cytokine whose secretion induced by L. monocytogenes depends upon phagosome escape, was also blocked by calpain inhibition. These data indicate that L. monocytogenes co-opts host calpain to facilitate its escape from the phagosome, and more generally, that calpain may represent a cellular Achilles heel exploited by pathogens.
format	article
author	Gloria Lopez-Castejon David Corbett Marie Goldrick Ian S Roberts David Brough
author_facet	Gloria Lopez-Castejon David Corbett Marie Goldrick Ian S Roberts David Brough
author_sort	Gloria Lopez-Castejon
title	Inhibition of calpain blocks the phagosomal escape of Listeria monocytogenes.
title_short	Inhibition of calpain blocks the phagosomal escape of Listeria monocytogenes.
title_full	Inhibition of calpain blocks the phagosomal escape of Listeria monocytogenes.
title_fullStr	Inhibition of calpain blocks the phagosomal escape of Listeria monocytogenes.
title_full_unstemmed	Inhibition of calpain blocks the phagosomal escape of Listeria monocytogenes.
title_sort	inhibition of calpain blocks the phagosomal escape of listeria monocytogenes.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/aa3e2fd0d13a4f7eaa44d8a8a6f27ffe
work_keys_str_mv	AT glorialopezcastejon inhibitionofcalpainblocksthephagosomalescapeoflisteriamonocytogenes AT davidcorbett inhibitionofcalpainblocksthephagosomalescapeoflisteriamonocytogenes AT mariegoldrick inhibitionofcalpainblocksthephagosomalescapeoflisteriamonocytogenes AT iansroberts inhibitionofcalpainblocksthephagosomalescapeoflisteriamonocytogenes AT davidbrough inhibitionofcalpainblocksthephagosomalescapeoflisteriamonocytogenes
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Inhibition of calpain blocks the phagosomal escape of Listeria monocytogenes.

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