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Small Rho GTPases and the Effector VipA Mediate the Invasion of Epithelial Cells by Filamentous Legionella pneumophila

Legionella pneumophila (Lp) exhibits different morphologies with varying degrees of virulence. Despite their detection in environmental sources of outbreaks and in respiratory tract secretions and lung autopsies from patients, the filamentous morphotype of Lp remains poorly studied. We previously de...

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Autores principales: Prashar, Akriti, Ortiz, María Eugenia, Lucarelli, Stefanie, Barker, Elizabeth, Tabatabeiyazdi, Zohreh, Shamoun, Feras, Raju, Deepa, Antonescu, Costin, Guyard, Cyril, Terebiznik, Mauricio R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5943596/
https://www.ncbi.nlm.nih.gov/pubmed/29774203
http://dx.doi.org/10.3389/fcimb.2018.00133
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author Prashar, Akriti
Ortiz, María Eugenia
Lucarelli, Stefanie
Barker, Elizabeth
Tabatabeiyazdi, Zohreh
Shamoun, Feras
Raju, Deepa
Antonescu, Costin
Guyard, Cyril
Terebiznik, Mauricio R.
author_facet Prashar, Akriti
Ortiz, María Eugenia
Lucarelli, Stefanie
Barker, Elizabeth
Tabatabeiyazdi, Zohreh
Shamoun, Feras
Raju, Deepa
Antonescu, Costin
Guyard, Cyril
Terebiznik, Mauricio R.
author_sort Prashar, Akriti
collection PubMed
description Legionella pneumophila (Lp) exhibits different morphologies with varying degrees of virulence. Despite their detection in environmental sources of outbreaks and in respiratory tract secretions and lung autopsies from patients, the filamentous morphotype of Lp remains poorly studied. We previously demonstrated that filamentous Lp invades lung epithelial cells (LECs) and replicates intracellularly in a Legionella containing vacuole. Filamentous Lp activates β1integrin and E-cadherin receptors at the surface of LECs leading to the formation of actin-rich cell membrane structures we termed hooks and membrane wraps. These structures entrap segments of an Lp filament on host cell surface and mediate bacterial internalization. Here we investigated the molecular mechanisms responsible for the actin rearrangements needed for the formation and elongation of these membrane wraps and bacterial internalization. We combined genetic and pharmacological approaches to assess the contribution of signaling downstream of β1integrin and E-cadherin receptors, and Lp Dot/Icm secretion system- translocated effectors toward the invasion process. Our studies demonstrate a multi-stage mechanism of LEC invasion by filamentous Lp. Bacterial attachment to host cells depends on signaling downstream of β1integrin and E-cadherin activation, leading to Rho GTPases-dependent activation of cellular actin nucleating proteins, Arp2/3 and mDia. This mediates the formation of primordial membrane wraps that entrap the filamentous bacteria on the cell surface. Following this, in a second phase of the invasion process the Dot/Icm translocated effector VipA mediates rapid membrane wrap elongation, leading to the engulfment of the filamentous bacteria by the LECs. Our findings provide the first description of Rho GTPases and a Dot/Icm effector VipA regulating the actin dynamics needed for the invasion of epithelial cells by Lp.
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spelling pubmed-59435962018-05-17 Small Rho GTPases and the Effector VipA Mediate the Invasion of Epithelial Cells by Filamentous Legionella pneumophila Prashar, Akriti Ortiz, María Eugenia Lucarelli, Stefanie Barker, Elizabeth Tabatabeiyazdi, Zohreh Shamoun, Feras Raju, Deepa Antonescu, Costin Guyard, Cyril Terebiznik, Mauricio R. Front Cell Infect Microbiol Microbiology Legionella pneumophila (Lp) exhibits different morphologies with varying degrees of virulence. Despite their detection in environmental sources of outbreaks and in respiratory tract secretions and lung autopsies from patients, the filamentous morphotype of Lp remains poorly studied. We previously demonstrated that filamentous Lp invades lung epithelial cells (LECs) and replicates intracellularly in a Legionella containing vacuole. Filamentous Lp activates β1integrin and E-cadherin receptors at the surface of LECs leading to the formation of actin-rich cell membrane structures we termed hooks and membrane wraps. These structures entrap segments of an Lp filament on host cell surface and mediate bacterial internalization. Here we investigated the molecular mechanisms responsible for the actin rearrangements needed for the formation and elongation of these membrane wraps and bacterial internalization. We combined genetic and pharmacological approaches to assess the contribution of signaling downstream of β1integrin and E-cadherin receptors, and Lp Dot/Icm secretion system- translocated effectors toward the invasion process. Our studies demonstrate a multi-stage mechanism of LEC invasion by filamentous Lp. Bacterial attachment to host cells depends on signaling downstream of β1integrin and E-cadherin activation, leading to Rho GTPases-dependent activation of cellular actin nucleating proteins, Arp2/3 and mDia. This mediates the formation of primordial membrane wraps that entrap the filamentous bacteria on the cell surface. Following this, in a second phase of the invasion process the Dot/Icm translocated effector VipA mediates rapid membrane wrap elongation, leading to the engulfment of the filamentous bacteria by the LECs. Our findings provide the first description of Rho GTPases and a Dot/Icm effector VipA regulating the actin dynamics needed for the invasion of epithelial cells by Lp. Frontiers Media S.A. 2018-05-03 /pmc/articles/PMC5943596/ /pubmed/29774203 http://dx.doi.org/10.3389/fcimb.2018.00133 Text en Copyright © 2018 Prashar, Ortiz, Lucarelli, Barker, Tabatabeiyazdi, Shamoun, Raju, Antonescu, Guyard and Terebiznik. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Prashar, Akriti
Ortiz, María Eugenia
Lucarelli, Stefanie
Barker, Elizabeth
Tabatabeiyazdi, Zohreh
Shamoun, Feras
Raju, Deepa
Antonescu, Costin
Guyard, Cyril
Terebiznik, Mauricio R.
Small Rho GTPases and the Effector VipA Mediate the Invasion of Epithelial Cells by Filamentous Legionella pneumophila
title Small Rho GTPases and the Effector VipA Mediate the Invasion of Epithelial Cells by Filamentous Legionella pneumophila
title_full Small Rho GTPases and the Effector VipA Mediate the Invasion of Epithelial Cells by Filamentous Legionella pneumophila
title_fullStr Small Rho GTPases and the Effector VipA Mediate the Invasion of Epithelial Cells by Filamentous Legionella pneumophila
title_full_unstemmed Small Rho GTPases and the Effector VipA Mediate the Invasion of Epithelial Cells by Filamentous Legionella pneumophila
title_short Small Rho GTPases and the Effector VipA Mediate the Invasion of Epithelial Cells by Filamentous Legionella pneumophila
title_sort small rho gtpases and the effector vipa mediate the invasion of epithelial cells by filamentous legionella pneumophila
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5943596/
https://www.ncbi.nlm.nih.gov/pubmed/29774203
http://dx.doi.org/10.3389/fcimb.2018.00133
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