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Activation of epidermal growth factor receptor is required for Chlamydia trachomatis development

BACKGROUND: Chlamydia trachomatis (C. trachomatis) is a clinically significant human pathogen and one of the leading causative agents of sexually transmitted diseases. As obligate intracellular bacteria, C. trachomatis has evolved strategies to redirect the host’s signaling and resources for its own...

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Autores principales: Patel, Achchhe L, Chen, Xiaofei, Wood, Scott T, Stuart, Elizabeth S, Arcaro, Kathleen F, Molina, Doris P, Petrovic, Snezana, Furdui, Cristina M, Tsang, Allen W
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4269859/
https://www.ncbi.nlm.nih.gov/pubmed/25471819
http://dx.doi.org/10.1186/s12866-014-0277-4
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author Patel, Achchhe L
Chen, Xiaofei
Wood, Scott T
Stuart, Elizabeth S
Arcaro, Kathleen F
Molina, Doris P
Petrovic, Snezana
Furdui, Cristina M
Tsang, Allen W
author_facet Patel, Achchhe L
Chen, Xiaofei
Wood, Scott T
Stuart, Elizabeth S
Arcaro, Kathleen F
Molina, Doris P
Petrovic, Snezana
Furdui, Cristina M
Tsang, Allen W
author_sort Patel, Achchhe L
collection PubMed
description BACKGROUND: Chlamydia trachomatis (C. trachomatis) is a clinically significant human pathogen and one of the leading causative agents of sexually transmitted diseases. As obligate intracellular bacteria, C. trachomatis has evolved strategies to redirect the host’s signaling and resources for its own survival and propagation. Despite the clinical notoriety of Chlamydia infections, the molecular interactions between C. trachomatis and its host cell proteins remain elusive. RESULTS: In this study, we focused on the involvement of the host cell epidermal growth factor receptor (EGFR) in C. trachomatis attachment and development. A combination of molecular approaches, pharmacological agents and cell lines were used to demonstrate distinct functional requirements of EGFR in C. trachomatis infection. We show that C. trachomatis increases the phosphorylation of EGFR and of its downstream effectors PLCγ1, Akt and STAT5. While both EGFR and platelet-derived growth factor receptor-β (PDGFRβ) are partially involved in bacterial attachment to the host cell surface, it is only the knockdown of EGFR and not PDGFRβ that affects the formation of C. trachomatis inclusions in the host cells. Inhibition of EGFR results in small immature inclusions, and prevents C. trachomatis-induced intracellular calcium mobilization and the assembly of the characteristic F-actin ring at the inclusion periphery. By using complementary approaches, we demonstrate that the coordinated regulation of both calcium mobilization and F-actin assembly by EGFR are necessary for maturation of chlamydial inclusion within the host cells. A particularly important finding of this study is the co-localization of EGFR with the F-actin at the periphery of C. trachomatis inclusion where it may function to nucleate the assembly of signaling protein complexes for cytoskeletal remodeling required for C. trachomatis development. CONCLUSION: Cumulatively, the data reported here connect the function of EGFR to C. trachomatis attachment and development in the host cells, and this could lead to new venues for targeting C. trachomatis infections and associated diseases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12866-014-0277-4) contains supplementary material, which is available to authorized users.
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spelling pubmed-42698592014-12-18 Activation of epidermal growth factor receptor is required for Chlamydia trachomatis development Patel, Achchhe L Chen, Xiaofei Wood, Scott T Stuart, Elizabeth S Arcaro, Kathleen F Molina, Doris P Petrovic, Snezana Furdui, Cristina M Tsang, Allen W BMC Microbiol Research Article BACKGROUND: Chlamydia trachomatis (C. trachomatis) is a clinically significant human pathogen and one of the leading causative agents of sexually transmitted diseases. As obligate intracellular bacteria, C. trachomatis has evolved strategies to redirect the host’s signaling and resources for its own survival and propagation. Despite the clinical notoriety of Chlamydia infections, the molecular interactions between C. trachomatis and its host cell proteins remain elusive. RESULTS: In this study, we focused on the involvement of the host cell epidermal growth factor receptor (EGFR) in C. trachomatis attachment and development. A combination of molecular approaches, pharmacological agents and cell lines were used to demonstrate distinct functional requirements of EGFR in C. trachomatis infection. We show that C. trachomatis increases the phosphorylation of EGFR and of its downstream effectors PLCγ1, Akt and STAT5. While both EGFR and platelet-derived growth factor receptor-β (PDGFRβ) are partially involved in bacterial attachment to the host cell surface, it is only the knockdown of EGFR and not PDGFRβ that affects the formation of C. trachomatis inclusions in the host cells. Inhibition of EGFR results in small immature inclusions, and prevents C. trachomatis-induced intracellular calcium mobilization and the assembly of the characteristic F-actin ring at the inclusion periphery. By using complementary approaches, we demonstrate that the coordinated regulation of both calcium mobilization and F-actin assembly by EGFR are necessary for maturation of chlamydial inclusion within the host cells. A particularly important finding of this study is the co-localization of EGFR with the F-actin at the periphery of C. trachomatis inclusion where it may function to nucleate the assembly of signaling protein complexes for cytoskeletal remodeling required for C. trachomatis development. CONCLUSION: Cumulatively, the data reported here connect the function of EGFR to C. trachomatis attachment and development in the host cells, and this could lead to new venues for targeting C. trachomatis infections and associated diseases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12866-014-0277-4) contains supplementary material, which is available to authorized users. BioMed Central 2014-12-04 /pmc/articles/PMC4269859/ /pubmed/25471819 http://dx.doi.org/10.1186/s12866-014-0277-4 Text en © Patel et al.; licensee BioMed Central Ltd. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Patel, Achchhe L
Chen, Xiaofei
Wood, Scott T
Stuart, Elizabeth S
Arcaro, Kathleen F
Molina, Doris P
Petrovic, Snezana
Furdui, Cristina M
Tsang, Allen W
Activation of epidermal growth factor receptor is required for Chlamydia trachomatis development
title Activation of epidermal growth factor receptor is required for Chlamydia trachomatis development
title_full Activation of epidermal growth factor receptor is required for Chlamydia trachomatis development
title_fullStr Activation of epidermal growth factor receptor is required for Chlamydia trachomatis development
title_full_unstemmed Activation of epidermal growth factor receptor is required for Chlamydia trachomatis development
title_short Activation of epidermal growth factor receptor is required for Chlamydia trachomatis development
title_sort activation of epidermal growth factor receptor is required for chlamydia trachomatis development
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4269859/
https://www.ncbi.nlm.nih.gov/pubmed/25471819
http://dx.doi.org/10.1186/s12866-014-0277-4
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