The Effector TepP Mediates Recruitment and Activation of Phosphoinositide 3-Kinase on Early <named-content content-type="genus-species">Chlamydia trachomatis</named-content> Vacuoles

ABSTRACT Chlamydia trachomatis delivers multiple type 3 secreted effector proteins to host epithelial cells to manipulate cytoskeletal functions, membrane dynamics, and signaling pathways. TepP is the most abundant effector protein secreted early in infection, but its molecular function is poorly un...

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Autores principales:	Victoria Carpenter, Yi-Shan Chen, Lee Dolat, Raphael H. Valdivia
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	CrkL PI3K PIP3 Src kinases T3S effector type I IFN Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/1a9812cd31a041fbade3db49bbc9394d
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spelling	oai:doaj.org-article:1a9812cd31a041fbade3db49bbc9394d2021-11-15T15:22:04ZThe Effector TepP Mediates Recruitment and Activation of Phosphoinositide 3-Kinase on Early <named-content content-type="genus-species">Chlamydia trachomatis</named-content> Vacuoles10.1128/mSphere.00207-172379-5042https://doaj.org/article/1a9812cd31a041fbade3db49bbc9394d2017-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00207-17https://doaj.org/toc/2379-5042ABSTRACT Chlamydia trachomatis delivers multiple type 3 secreted effector proteins to host epithelial cells to manipulate cytoskeletal functions, membrane dynamics, and signaling pathways. TepP is the most abundant effector protein secreted early in infection, but its molecular function is poorly understood. In this report, we provide evidence that TepP is important for bacterial replication in cervical epithelial cells, activation of type I IFN genes, and recruitment of class I phosphoinositide 3-kinases (PI3K) and signaling adaptor protein CrkL to nascent pathogen-containing vacuoles (inclusions). We also show that TepP is a target of tyrosine phosphorylation by Src kinases but that these modifications do not appear to influence the recruitment of PI3K or CrkL. The translocation of TepP correlated with an increase in the intracellular pools of phosphoinositide-(3,4,5)-triphosphate but not the activation of the prosurvival kinase Akt, suggesting that TepP-mediated activation of PI3K is spatially restricted to early inclusions. Furthermore, we linked PI3K activity to the dampening of transcription of type I interferon (IFN)-induced genes early in infection. Overall, these findings indicate that TepP can modulate cell signaling and, potentially, membrane trafficking events by spatially restricted activation of PI3K. IMPORTANCE This article shows that Chlamydia recruits PI3K, an enzyme important for host cell survival and internal membrane functions, to the pathogens inside cells by secreting a scaffolding protein called TepP. TepP enhances Chlamydia replication and dampens the activation of immune responses.Victoria CarpenterYi-Shan ChenLee DolatRaphael H. ValdiviaAmerican Society for MicrobiologyarticleCrkLPI3KPIP3Src kinasesT3S effectortype I IFNMicrobiologyQR1-502ENmSphere, Vol 2, Iss 4 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	CrkL PI3K PIP3 Src kinases T3S effector type I IFN Microbiology QR1-502
spellingShingle	CrkL PI3K PIP3 Src kinases T3S effector type I IFN Microbiology QR1-502 Victoria Carpenter Yi-Shan Chen Lee Dolat Raphael H. Valdivia The Effector TepP Mediates Recruitment and Activation of Phosphoinositide 3-Kinase on Early <named-content content-type="genus-species">Chlamydia trachomatis</named-content> Vacuoles
description	ABSTRACT Chlamydia trachomatis delivers multiple type 3 secreted effector proteins to host epithelial cells to manipulate cytoskeletal functions, membrane dynamics, and signaling pathways. TepP is the most abundant effector protein secreted early in infection, but its molecular function is poorly understood. In this report, we provide evidence that TepP is important for bacterial replication in cervical epithelial cells, activation of type I IFN genes, and recruitment of class I phosphoinositide 3-kinases (PI3K) and signaling adaptor protein CrkL to nascent pathogen-containing vacuoles (inclusions). We also show that TepP is a target of tyrosine phosphorylation by Src kinases but that these modifications do not appear to influence the recruitment of PI3K or CrkL. The translocation of TepP correlated with an increase in the intracellular pools of phosphoinositide-(3,4,5)-triphosphate but not the activation of the prosurvival kinase Akt, suggesting that TepP-mediated activation of PI3K is spatially restricted to early inclusions. Furthermore, we linked PI3K activity to the dampening of transcription of type I interferon (IFN)-induced genes early in infection. Overall, these findings indicate that TepP can modulate cell signaling and, potentially, membrane trafficking events by spatially restricted activation of PI3K. IMPORTANCE This article shows that Chlamydia recruits PI3K, an enzyme important for host cell survival and internal membrane functions, to the pathogens inside cells by secreting a scaffolding protein called TepP. TepP enhances Chlamydia replication and dampens the activation of immune responses.
format	article
author	Victoria Carpenter Yi-Shan Chen Lee Dolat Raphael H. Valdivia
author_facet	Victoria Carpenter Yi-Shan Chen Lee Dolat Raphael H. Valdivia
author_sort	Victoria Carpenter
title	The Effector TepP Mediates Recruitment and Activation of Phosphoinositide 3-Kinase on Early <named-content content-type="genus-species">Chlamydia trachomatis</named-content> Vacuoles
title_short	The Effector TepP Mediates Recruitment and Activation of Phosphoinositide 3-Kinase on Early <named-content content-type="genus-species">Chlamydia trachomatis</named-content> Vacuoles
title_full	The Effector TepP Mediates Recruitment and Activation of Phosphoinositide 3-Kinase on Early <named-content content-type="genus-species">Chlamydia trachomatis</named-content> Vacuoles
title_fullStr	The Effector TepP Mediates Recruitment and Activation of Phosphoinositide 3-Kinase on Early <named-content content-type="genus-species">Chlamydia trachomatis</named-content> Vacuoles
title_full_unstemmed	The Effector TepP Mediates Recruitment and Activation of Phosphoinositide 3-Kinase on Early <named-content content-type="genus-species">Chlamydia trachomatis</named-content> Vacuoles
title_sort	effector tepp mediates recruitment and activation of phosphoinositide 3-kinase on early <named-content content-type="genus-species">chlamydia trachomatis</named-content> vacuoles
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/1a9812cd31a041fbade3db49bbc9394d
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The Effector TepP Mediates Recruitment and Activation of Phosphoinositide 3-Kinase on Early <named-content content-type="genus-species">Chlamydia trachomatis</named-content> Vacuoles

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