The Effector TepP Mediates Recruitment and Activation of Phosphoinositide 3-Kinase on Early Chlamydia trachomatis Vacuoles.

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Carpenter, V; Chen, Y-S; Dolat, L; Valdivia, RH

Published Date

  • July 2017

Published In

Volume / Issue

  • 2 / 4

PubMed ID

  • 28744480

Pubmed Central ID

  • 28744480

International Standard Serial Number (ISSN)

  • 2379-5042

Digital Object Identifier (DOI)

  • 10.1128/mSphere.00207-17

Language

  • eng

Conference Location

  • United States