# Mechanisms and significance of intestinal cell proliferation in Vibrio parahaemolyticus infection

> **NIH NIH R01** · UNIVERSITY OF CONNECTICUT STORRS · 2020 · $238,837

## Abstract

PROJECT SUMMARY
Vibrio parahaemolyticus is a leading cause of seafood-borne diarrheal disease and a multidrug resistant
emerging pathogen. Although it is known that one of the type 3 secretion systems (T3SS2) plays an essential
role in bacterial colonization and diarrheal disease, the assembly of a functional T3SS2 apparatus and the
effectors that are responsible for pathological alterations during infection are not completely defined. Continued
existence of this gap represents an important problem because, until it is filled, the likelihood that
pharmacological intervention of V. parahaemolyticus infection by targeting specific virulence factors is remote.
The long-term goal is to harness the medical benefits that are offered by defining T3SS2 apparatus assembly
and the function of effector proteins during V. parahaemolyticus infection. The overall objective here is to
identify proteins that are required for the assembly of functional T3SS2 apparatus and enhancing intestinal cell
proliferation. The central hypothesis is that VopI, an essential component for the assembly of functional T3SS2
apparatus, also serves as an effector protein to regulate intestinal cell proliferation for the benefit of intestinal
colonization. This hypothesis has been formulated on the basis of our own preliminary data that deletion of
VopI blocked the secretion and translocation of T3SS2 substrates and VopI itself can be translocated by
T3SS2 into host cell nucleus to regulate cell proliferation and bacterial colonization. The rationale for the
proposed research is that, once the role of VopI in the assembly of T3SS2 apparatus and epithelial cell
proliferation is elucidated, both T3SS2 assembly and intestinal epithelial cell proliferation could be
pharmacologically modulated, resulting in new and innovative approaches for the prevention and treatment of
infection with V. parahaemolyticus. Furthermore, the results obtained from this study will shed new light on the
role of T3SS apparatus protein as an effector both in vitro and in vivo during bacterial infection. Guided by
strong preliminary data, this hypothesis will be tested by pursuing three specific aims: 1) Define the role of VopI
as a structural component in the assembly of T3SS2 apparatus; 2) Define the mechanisms by which VopI, as
an effector, promotes cell proliferation; and 3) Define the role of VopI as an effector in vivo using an infant
rabbit model. In the first aim, we will determine VopI localization, its interaction partners within the T3SS2
apparatus and its effect on T3SS2 biogenesis using electron microscopy, confocal microscopy and
biochemical approaches. In the second aim, we will elucidate the mechanism of VopI-mediated cell
proliferation. Particularly, we will determine the biological significance of the interaction between VopI and a
host nucleolar protein, EBP2. In the third aim, we will determine the role of VopI, as an effector, in intestinal cell
proliferation in vivo and the contribution of...

## Key facts

- **NIH application ID:** 10017647
- **Project number:** 5R01AI125291-04
- **Recipient organization:** UNIVERSITY OF CONNECTICUT STORRS
- **Principal Investigator:** Steven J Geary
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $238,837
- **Award type:** 5
- **Project period:** 2017-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10017647

## Citation

> US National Institutes of Health, RePORTER application 10017647, Mechanisms and significance of intestinal cell proliferation in Vibrio parahaemolyticus infection (5R01AI125291-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10017647. Licensed CC0.

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