Invasion of the Brain by <italic toggle="yes">Listeria monocytogenes</italic> Is Mediated by InlF and Host Cell Vimentin

ABSTRACT Listeria monocytogenes is a facultative intracellular bacterial pathogen that is frequently associated with food-borne infection. Of particular concern is the ability of L. monocytogenes to breach the blood-brain barrier, leading to life-threatening meningitis and encephalitis. The mechanis...

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Autores principales: Pallab Ghosh, Elizabeth M. Halvorsen, Dustin A. Ammendolia, Nirit Mor-Vaknin, Mary X. D. O’Riordan, John H. Brumell, David M. Markovitz, Darren E. Higgins
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Publicado: American Society for Microbiology 2018
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spelling oai:doaj.org-article:3987dc4dc043403987c170c9dc79fd392021-11-15T15:53:25ZInvasion of the Brain by <italic toggle="yes">Listeria monocytogenes</italic> Is Mediated by InlF and Host Cell Vimentin10.1128/mBio.00160-182150-7511https://doaj.org/article/3987dc4dc043403987c170c9dc79fd392018-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00160-18https://doaj.org/toc/2150-7511ABSTRACT Listeria monocytogenes is a facultative intracellular bacterial pathogen that is frequently associated with food-borne infection. Of particular concern is the ability of L. monocytogenes to breach the blood-brain barrier, leading to life-threatening meningitis and encephalitis. The mechanisms used by bacterial pathogens to infect the brain are not fully understood. Here we show that L. monocytogenes is able to utilize vimentin for invasion of host cells. Vimentin is a type III intermediate filament protein within the cytosol but is also expressed on the host cell surface. We found that L. monocytogenes interaction with surface-localized vimentin promoted bacterial uptake. Furthermore, in the absence of vimentin, L. monocytogenes colonization of the brain was severely compromised in mice. The L. monocytogenes virulence factor InlF was found to bind vimentin and was necessary for optimal bacterial colonization of the brain. These studies reveal a novel receptor-ligand interaction that enhances infection of the brain by L. monocytogenes and highlights the importance of surface vimentin in host-pathogen interactions. IMPORTANCE Listeria monocytogenes is an intracellular bacterial pathogen that is capable of invading numerous host cells during infection. L. monocytogenes can cross the blood-brain barrier, leading to life-threatening meningitis. Here we show that an L. monocytogenes surface protein, InlF, is necessary for optimal colonization of the brain in mice. Furthermore, in the absence of vimentin, a cytosolic intermediate filament protein that is also present on the surface of brain endothelial cells, colonization of the brain was significantly impaired. We further show that InlF binds vimentin to mediate invasion of host cells. This work identifies InlF as a bacterial surface protein with specific relevance for infection of the brain and underscores the significance of host cell surface vimentin interactions in microbial pathogenesis.Pallab GhoshElizabeth M. HalvorsenDustin A. AmmendoliaNirit Mor-VakninMary X. D. O’RiordanJohn H. BrumellDavid M. MarkovitzDarren E. HigginsAmerican Society for MicrobiologyarticleInlFListeria monocytogenesadhesionbraininvasionmeningitisMicrobiologyQR1-502ENmBio, Vol 9, Iss 1 (2018)
institution DOAJ
collection DOAJ
language EN
topic InlF
Listeria monocytogenes
adhesion
brain
invasion
meningitis
Microbiology
QR1-502
spellingShingle InlF
Listeria monocytogenes
adhesion
brain
invasion
meningitis
Microbiology
QR1-502
Pallab Ghosh
Elizabeth M. Halvorsen
Dustin A. Ammendolia
Nirit Mor-Vaknin
Mary X. D. O’Riordan
John H. Brumell
David M. Markovitz
Darren E. Higgins
Invasion of the Brain by <italic toggle="yes">Listeria monocytogenes</italic> Is Mediated by InlF and Host Cell Vimentin
description ABSTRACT Listeria monocytogenes is a facultative intracellular bacterial pathogen that is frequently associated with food-borne infection. Of particular concern is the ability of L. monocytogenes to breach the blood-brain barrier, leading to life-threatening meningitis and encephalitis. The mechanisms used by bacterial pathogens to infect the brain are not fully understood. Here we show that L. monocytogenes is able to utilize vimentin for invasion of host cells. Vimentin is a type III intermediate filament protein within the cytosol but is also expressed on the host cell surface. We found that L. monocytogenes interaction with surface-localized vimentin promoted bacterial uptake. Furthermore, in the absence of vimentin, L. monocytogenes colonization of the brain was severely compromised in mice. The L. monocytogenes virulence factor InlF was found to bind vimentin and was necessary for optimal bacterial colonization of the brain. These studies reveal a novel receptor-ligand interaction that enhances infection of the brain by L. monocytogenes and highlights the importance of surface vimentin in host-pathogen interactions. IMPORTANCE Listeria monocytogenes is an intracellular bacterial pathogen that is capable of invading numerous host cells during infection. L. monocytogenes can cross the blood-brain barrier, leading to life-threatening meningitis. Here we show that an L. monocytogenes surface protein, InlF, is necessary for optimal colonization of the brain in mice. Furthermore, in the absence of vimentin, a cytosolic intermediate filament protein that is also present on the surface of brain endothelial cells, colonization of the brain was significantly impaired. We further show that InlF binds vimentin to mediate invasion of host cells. This work identifies InlF as a bacterial surface protein with specific relevance for infection of the brain and underscores the significance of host cell surface vimentin interactions in microbial pathogenesis.
format article
author Pallab Ghosh
Elizabeth M. Halvorsen
Dustin A. Ammendolia
Nirit Mor-Vaknin
Mary X. D. O’Riordan
John H. Brumell
David M. Markovitz
Darren E. Higgins
author_facet Pallab Ghosh
Elizabeth M. Halvorsen
Dustin A. Ammendolia
Nirit Mor-Vaknin
Mary X. D. O’Riordan
John H. Brumell
David M. Markovitz
Darren E. Higgins
author_sort Pallab Ghosh
title Invasion of the Brain by <italic toggle="yes">Listeria monocytogenes</italic> Is Mediated by InlF and Host Cell Vimentin
title_short Invasion of the Brain by <italic toggle="yes">Listeria monocytogenes</italic> Is Mediated by InlF and Host Cell Vimentin
title_full Invasion of the Brain by <italic toggle="yes">Listeria monocytogenes</italic> Is Mediated by InlF and Host Cell Vimentin
title_fullStr Invasion of the Brain by <italic toggle="yes">Listeria monocytogenes</italic> Is Mediated by InlF and Host Cell Vimentin
title_full_unstemmed Invasion of the Brain by <italic toggle="yes">Listeria monocytogenes</italic> Is Mediated by InlF and Host Cell Vimentin
title_sort invasion of the brain by <italic toggle="yes">listeria monocytogenes</italic> is mediated by inlf and host cell vimentin
publisher American Society for Microbiology
publishDate 2018
url https://doaj.org/article/3987dc4dc043403987c170c9dc79fd39
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