# Functional characterization of early Chlamydia effectors

> **NIH NIH R01** · DUKE UNIVERSITY · 2021 · $484,647

## Abstract

Project Description/Summary/Abstract
 The obligate intracellular bacterium Chlamydia trachomatis is a widely disseminated obligate
pathogen that infects epithelial surfaces of the urogenital tract, leading to severe sequela such as pelvic
inflammatory disease, and infertility. During the initial stages of infection Chlamydia likely delivers
between 10-15 separate Type III secreted (T3S) “effector” proteins into the target host cell. We
hypothesize that these Chlamydia effector proteins work co-operatively to temporally reprogram
signaling pathways and cytoskeletal functions to promote cell invasion and establish a nascent
pathogenic vacuole (“inclusion”)
 In our first aim, we propose to apply emerging genetic and molecular genetic tools in Chlamydia to
define the role of early effectors play in invasion, inclusion maturation and in vivo infections. We also
propose to perform an epistatic analysis of combinations of effector mutants to group effector by
functional groups and to prioritize a detailed molecular characterization of effector that are central
signaling nodes.
 In our second aim, we focus on the characterization of Tepp, an effector that plays important roles
in reprograming signaling pathways, including those involved in innate immune responses. We propose
to define the mechanism of activation of Class I phosphoinositide 3 kinases (PI3K) at nascent
inclusions and the role these activities play in the regulation of membrane dynamics and activation of
Type I interferon responses. In parallel, we will identify the molecular players that lead to the Tepp-
mediated activation and modification of Eps8, a regulator of Rac1 activity and cell-cell junctions, by
applying “proximity proteomics” approaches.
 Overall, our research plan seeks to perform both a systems levels assessment of the function of
early effectors and a detailed molecular characterization of mechanism of action for selected effectors.
The overall goal is to define the molecular basis of how specific effector(s) function, identify how
signaling pathways are re-programmed and how they all ultimately contribute to Chlamydia survival in
host tissues and the induction of pathology.

## Key facts

- **NIH application ID:** 10170218
- **Project number:** 5R01AI134891-04
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Raphael H Valdivia
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $484,647
- **Award type:** 5
- **Project period:** 2018-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10170218

## Citation

> US National Institutes of Health, RePORTER application 10170218, Functional characterization of early Chlamydia effectors (5R01AI134891-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10170218. Licensed CC0.

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