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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-05-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fcimb.2018.00133/full |
| _version_ | 1811275090797527040 |
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| author | Akriti Prashar Akriti Prashar María Eugenia Ortiz Stefanie Lucarelli Elizabeth Barker Elizabeth Barker Zohreh Tabatabeiyazdi Zohreh Tabatabeiyazdi Feras Shamoun Deepa Raju Costin Antonescu Cyril Guyard Cyril Guyard Mauricio R. Terebiznik Mauricio R. Terebiznik |
| author_facet | Akriti Prashar Akriti Prashar María Eugenia Ortiz Stefanie Lucarelli Elizabeth Barker Elizabeth Barker Zohreh Tabatabeiyazdi Zohreh Tabatabeiyazdi Feras Shamoun Deepa Raju Costin Antonescu Cyril Guyard Cyril Guyard Mauricio R. Terebiznik Mauricio R. Terebiznik |
| author_sort | Akriti Prashar |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T23:31:51Z |
| format | Article |
| id | doaj.art-bf05940548fc4900bc77d51c5d3003c0 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-04-12T23:31:51Z |
| publishDate | 2018-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-bf05940548fc4900bc77d51c5d3003c02022-12-22T03:12:16ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882018-05-01810.3389/fcimb.2018.00133344879Small Rho GTPases and the Effector VipA Mediate the Invasion of Epithelial Cells by Filamentous Legionella pneumophilaAkriti Prashar0Akriti Prashar1María Eugenia Ortiz2Stefanie Lucarelli3Elizabeth Barker4Elizabeth Barker5Zohreh Tabatabeiyazdi6Zohreh Tabatabeiyazdi7Feras Shamoun8Deepa Raju9Costin Antonescu10Cyril Guyard11Cyril Guyard12Mauricio R. Terebiznik13Mauricio R. Terebiznik14Department of Biological Sciences, University of Toronto at Scarborough, Scarborough, ON, CanadaDepartment of Cell and Systems Biology, University of Toronto, Toronto, ON, CanadaDepartment of Biological Sciences, University of Toronto at Scarborough, Scarborough, ON, CanadaDepartment of Chemistry and Biology, Ryerson University, Toronto, ON, CanadaDepartment of Biological Sciences, University of Toronto at Scarborough, Scarborough, ON, CanadaDepartment of Cell and Systems Biology, University of Toronto, Toronto, ON, CanadaDepartment of Biological Sciences, University of Toronto at Scarborough, Scarborough, ON, CanadaDepartment of Cell and Systems Biology, University of Toronto, Toronto, ON, CanadaDepartment of Biological Sciences, University of Toronto at Scarborough, Scarborough, ON, CanadaDepartment of Biological Sciences, University of Toronto at Scarborough, Scarborough, ON, CanadaDepartment of Chemistry and Biology, Ryerson University, Toronto, ON, CanadaBioaster, Lyon, FranceMolecular Microbiology, Public Health Ontario, Toronto, ON, CanadaDepartment of Biological Sciences, University of Toronto at Scarborough, Scarborough, ON, CanadaDepartment of Cell and Systems Biology, University of Toronto, Toronto, ON, CanadaLegionella 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.http://journal.frontiersin.org/article/10.3389/fcimb.2018.00133/fullLegionella pneumophilaRho GTPasesactinVipAfilamentous bacteria |
| spellingShingle | Akriti Prashar Akriti Prashar María Eugenia Ortiz Stefanie Lucarelli Elizabeth Barker Elizabeth Barker Zohreh Tabatabeiyazdi Zohreh Tabatabeiyazdi Feras Shamoun Deepa Raju Costin Antonescu Cyril Guyard Cyril Guyard Mauricio R. Terebiznik Mauricio R. Terebiznik Small Rho GTPases and the Effector VipA Mediate the Invasion of Epithelial Cells by Filamentous Legionella pneumophila Frontiers in Cellular and Infection Microbiology Legionella pneumophila Rho GTPases actin VipA filamentous bacteria |
| 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 | Legionella pneumophila Rho GTPases actin VipA filamentous bacteria |
| url | http://journal.frontiersin.org/article/10.3389/fcimb.2018.00133/full |
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