GTPases of the Rho subfamily are required for Brucella abortus internalization in nonprofessional phagocytes: direct activation of Cdc42
Members of the genus Brucella are intracellular alpha-Proteobacteria responsible for brucellosis, a chronic disease of humans and animals. Little is known about Brucella virulence mechanisms, but the abilities of these bacteria to invade and to survive within cells are decisive factors for causing d...
| Autores: | , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2001 |
| País: | España |
| Institución: | Universidad de Navarra |
| Repositorio: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Idioma: | inglés |
| OAI Identifier: | oai:dadun.unav.edu:10171/66205 |
| Acceso en línea: | https://hdl.handle.net/10171/66205 |
| Access Level: | acceso abierto |
| Palabra clave: | Brucellosi Zoonosis Brucella |
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GTPases of the Rho subfamily are required for Brucella abortus internalization in nonprofessional phagocytes: direct activation of Cdc42Guzman-Verri, C. (Caterina)|||/items/8608bab4-b31a-4c53-b441-c2a0b6d93554Chaves-Olarte, E. (Esteban)|||/items/dafc39e3-e04f-4c8b-bf17-70eb2e1d1aafEichel-Streiber, C. (Christoph) von|||/items/f1ba8f3a-1d3b-46da-bdab-4b2dabaeca9cLópez-Goñi, I. (Ignacio)|||/items/228678b8-8965-4c7c-aa6f-493277285d88Thelestam, M. (Monica)|||/items/2b87cb07-b831-401b-bce7-b9dd85000976Arvidson, S. (Staffan)|||/items/4b8ac5bd-5811-4dbb-9d1e-540e54c5214aGorvel, J.P. (Jean Pierre)|||/items/b754f278-d985-4792-9319-e9fc71f1cb11Moreno, E. (Edgardo)|||/items/11186877-6440-423f-a77a-c63ec45c54b0BrucellosiZoonosisBrucellaMembers of the genus Brucella are intracellular alpha-Proteobacteria responsible for brucellosis, a chronic disease of humans and animals. Little is known about Brucella virulence mechanisms, but the abilities of these bacteria to invade and to survive within cells are decisive factors for causing disease. Transmission electron and fluorescence microscopy of infected nonprofessional phagocytic HeLa cells revealed minor membrane changes accompanied by discrete recruitment of F-actin at the site of Brucella abortus entry. Cell uptake of B. abortus was negatively affected to various degrees by actin, actin-myosin, and microtubule chemical inhibitors. Modulators of MAPKs and protein-tyrosine kinases hampered Brucella cell internalization. Inactivation of Rho small GTPases using clostridial toxins TcdB-10463, TcdB-1470, TcsL-1522, and TcdA significantly reduced the uptake of B. abortus by HeLa cells. In contrast, cytotoxic necrotizing factor from Escherichia coli, known to activate Rho, Rac, and Cdc42 small GTPases, increased the internalization of both virulent and non-virulent B. abortus. Expression of dominant-positive Rho, Rac, and Cdc42 forms in HeLa cells promoted the uptake of B. abortus, whereas expression of dominant-negative forms of these GTPases in HeLa cells hampered Brucella uptake. Cdc42 was activated upon cell contact by virulent B. abortus, but not by a noninvasive isogenic strain, as proven by affinity precipitation of active Rho, Rac, and Cdc42. The polyphasic approach used to discern the molecular events leading to Brucella internalization provides new alternatives for exploring the complexity of the signals required by intracellular pathogens for cell invasion.Dadun. Depósito Académico Digital Universidad de Navarra20232023-05-1020012001-01-0120012001-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/66205reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/662052026-06-21T12:47:57Z |
| dc.title.none.fl_str_mv |
GTPases of the Rho subfamily are required for Brucella abortus internalization in nonprofessional phagocytes: direct activation of Cdc42 |
| title |
GTPases of the Rho subfamily are required for Brucella abortus internalization in nonprofessional phagocytes: direct activation of Cdc42 |
| spellingShingle |
GTPases of the Rho subfamily are required for Brucella abortus internalization in nonprofessional phagocytes: direct activation of Cdc42 Guzman-Verri, C. (Caterina)|||/items/8608bab4-b31a-4c53-b441-c2a0b6d93554 Brucellosi Zoonosis Brucella |
| title_short |
GTPases of the Rho subfamily are required for Brucella abortus internalization in nonprofessional phagocytes: direct activation of Cdc42 |
| title_full |
GTPases of the Rho subfamily are required for Brucella abortus internalization in nonprofessional phagocytes: direct activation of Cdc42 |
| title_fullStr |
GTPases of the Rho subfamily are required for Brucella abortus internalization in nonprofessional phagocytes: direct activation of Cdc42 |
| title_full_unstemmed |
GTPases of the Rho subfamily are required for Brucella abortus internalization in nonprofessional phagocytes: direct activation of Cdc42 |
| title_sort |
GTPases of the Rho subfamily are required for Brucella abortus internalization in nonprofessional phagocytes: direct activation of Cdc42 |
| dc.creator.none.fl_str_mv |
Guzman-Verri, C. (Caterina)|||/items/8608bab4-b31a-4c53-b441-c2a0b6d93554 Chaves-Olarte, E. (Esteban)|||/items/dafc39e3-e04f-4c8b-bf17-70eb2e1d1aaf Eichel-Streiber, C. (Christoph) von|||/items/f1ba8f3a-1d3b-46da-bdab-4b2dabaeca9c López-Goñi, I. (Ignacio)|||/items/228678b8-8965-4c7c-aa6f-493277285d88 Thelestam, M. (Monica)|||/items/2b87cb07-b831-401b-bce7-b9dd85000976 Arvidson, S. (Staffan)|||/items/4b8ac5bd-5811-4dbb-9d1e-540e54c5214a Gorvel, J.P. (Jean Pierre)|||/items/b754f278-d985-4792-9319-e9fc71f1cb11 Moreno, E. (Edgardo)|||/items/11186877-6440-423f-a77a-c63ec45c54b0 |
| author |
Guzman-Verri, C. (Caterina)|||/items/8608bab4-b31a-4c53-b441-c2a0b6d93554 |
| author_facet |
Guzman-Verri, C. (Caterina)|||/items/8608bab4-b31a-4c53-b441-c2a0b6d93554 Chaves-Olarte, E. (Esteban)|||/items/dafc39e3-e04f-4c8b-bf17-70eb2e1d1aaf Eichel-Streiber, C. (Christoph) von|||/items/f1ba8f3a-1d3b-46da-bdab-4b2dabaeca9c López-Goñi, I. (Ignacio)|||/items/228678b8-8965-4c7c-aa6f-493277285d88 Thelestam, M. (Monica)|||/items/2b87cb07-b831-401b-bce7-b9dd85000976 Arvidson, S. (Staffan)|||/items/4b8ac5bd-5811-4dbb-9d1e-540e54c5214a Gorvel, J.P. (Jean Pierre)|||/items/b754f278-d985-4792-9319-e9fc71f1cb11 Moreno, E. (Edgardo)|||/items/11186877-6440-423f-a77a-c63ec45c54b0 |
| author_role |
author |
| author2 |
Chaves-Olarte, E. (Esteban)|||/items/dafc39e3-e04f-4c8b-bf17-70eb2e1d1aaf Eichel-Streiber, C. (Christoph) von|||/items/f1ba8f3a-1d3b-46da-bdab-4b2dabaeca9c López-Goñi, I. (Ignacio)|||/items/228678b8-8965-4c7c-aa6f-493277285d88 Thelestam, M. (Monica)|||/items/2b87cb07-b831-401b-bce7-b9dd85000976 Arvidson, S. (Staffan)|||/items/4b8ac5bd-5811-4dbb-9d1e-540e54c5214a Gorvel, J.P. (Jean Pierre)|||/items/b754f278-d985-4792-9319-e9fc71f1cb11 Moreno, E. (Edgardo)|||/items/11186877-6440-423f-a77a-c63ec45c54b0 |
| author2_role |
author author author author author author author |
| dc.contributor.none.fl_str_mv |
Dadun. Depósito Académico Digital Universidad de Navarra |
| dc.subject.none.fl_str_mv |
Brucellosi Zoonosis Brucella |
| topic |
Brucellosi Zoonosis Brucella |
| description |
Members of the genus Brucella are intracellular alpha-Proteobacteria responsible for brucellosis, a chronic disease of humans and animals. Little is known about Brucella virulence mechanisms, but the abilities of these bacteria to invade and to survive within cells are decisive factors for causing disease. Transmission electron and fluorescence microscopy of infected nonprofessional phagocytic HeLa cells revealed minor membrane changes accompanied by discrete recruitment of F-actin at the site of Brucella abortus entry. Cell uptake of B. abortus was negatively affected to various degrees by actin, actin-myosin, and microtubule chemical inhibitors. Modulators of MAPKs and protein-tyrosine kinases hampered Brucella cell internalization. Inactivation of Rho small GTPases using clostridial toxins TcdB-10463, TcdB-1470, TcsL-1522, and TcdA significantly reduced the uptake of B. abortus by HeLa cells. In contrast, cytotoxic necrotizing factor from Escherichia coli, known to activate Rho, Rac, and Cdc42 small GTPases, increased the internalization of both virulent and non-virulent B. abortus. Expression of dominant-positive Rho, Rac, and Cdc42 forms in HeLa cells promoted the uptake of B. abortus, whereas expression of dominant-negative forms of these GTPases in HeLa cells hampered Brucella uptake. Cdc42 was activated upon cell contact by virulent B. abortus, but not by a noninvasive isogenic strain, as proven by affinity precipitation of active Rho, Rac, and Cdc42. The polyphasic approach used to discern the molecular events leading to Brucella internalization provides new alternatives for exploring the complexity of the signals required by intracellular pathogens for cell invasion. |
| publishDate |
2001 |
| dc.date.none.fl_str_mv |
2001 2001-01-01 2001 2001-01-01 2023 2023-05-10 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/10171/66205 |
| url |
https://hdl.handle.net/10171/66205 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 |
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openAccess |
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application/pdf |
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reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra instname:Universidad de Navarra |
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Universidad de Navarra |
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Dadun. Depósito Académico Digital de la Universidad de Navarra |
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Dadun. Depósito Académico Digital de la Universidad de Navarra |
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1869407162306920448 |
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15.300719 |