# Molecular and Cellular Dissection of Campylobacter Jejuni Effector Protein Function

> **NIH NIH R01** · WASHINGTON STATE UNIVERSITY · 2020 · $377,193

## Abstract

Title: Modulation of Host Cell Function by Campylobacter jejuni Effector Proteins
Project Summary
Infection with Campylobacter jejuni is responsible for millions of cases of diarrhea per year and is associated
with Guillain-Barré syndrome, the leading cause of flaccid paralysis in the post-polio era. Although researchers
have surmised for more than two decades that C. jejuni-mediated enteritis is dependent on invasion of the cells
lining the gastrointestinal tract and is accompanied by a robust inflammatory response, the pathogen and host
responses that contribute to C. jejuni-mediated enteritis are ill-defined. My lab discovered that this pathogen-
induced event (cell invasion) requires the delivery of proteins from C. jejuni to the cytosol of host cells. We
have designated these secreted proteins the Campylobacter invasion antigens (Cia). The Cia proteins co-opt
components of the focal complex (a cell-matrix adhesion structure) and the MEK/ERK signaling pathway to
trigger membrane ruffling (lamellipodia and filopodia extensions – cellular protrusions supported by actin
filaments). Our overall goal is to identify the mechanism(s) that C. jejuni utilizes to subvert components of the
focal complex (FC) to promote cell invasion through cytoskeletal reorganization. Contextually, these studies
will provide insight into how microbes modulate cellular signaling pathways to favor pathogen survival and
dissemination.
We have shown that the CiaC and CiaD effectors are necessary for C. jejuni cellular invasion. Our working
hypothesis is that these two effectors contain domains that direct the formation of the Campylobacter invasion
complex. More specifically, we hypothesize that CiaC and CiaD co-opt components of the FC and FC-
associated proteins that enable the cross-talk (convergence) of cellular pathways and trigger cytoskeletal
reorganization and chemokine production (IL-8) in host cells. The precise mechanism(s) that CiaC and CiaD
use to modulate cytoskeletal rearrangement and bacterial uptake are not known. Thus, our goal of elucidating
how the CiaC and CiaD effectors drive C. jejuni-cell invasion and chemokine induction is essential for
understanding the molecular and cellular basis of C. jejuni-mediated enteritis and is a prerequisite for the
development of targeted methods to prevent and treat C. jejuni disease.
The Specific Aims of this proposal are to:
1) Establish the host cell targets of both CiaC and CiaD;
2) Identify the host cell proteins phosphorylated in a CiaC- and CiaD-dependent manner and determine the
 role of these phosphorylation events in modulating host cell signaling pathways; and
3) Test whether the C. jejuni CiaC and CiaD effectors are required for disease in piglets and determine if
 deficiency of either protein results in a unique disease phenotype.

## Key facts

- **NIH application ID:** 9930025
- **Project number:** 5R01AI125356-05
- **Recipient organization:** WASHINGTON STATE UNIVERSITY
- **Principal Investigator:** Michael E Konkel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $377,193
- **Award type:** 5
- **Project period:** 2016-06-16 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9930025

## Citation

> US National Institutes of Health, RePORTER application 9930025, Molecular and Cellular Dissection of Campylobacter Jejuni Effector Protein Function (5R01AI125356-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9930025. Licensed CC0.

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