# Role of the T3SS  effector protein IcsB in Shigella flexneri infection

> **NIH NIH F31** · UNIVERSITY OF VIRGINIA · 2020 · $34,187

## Abstract

PROJECT SUMMARY/ABSTRACT
Shigella flexneri is a human pathogen that causes shigellosis, a severe diarrheal disease. S. flexneri invades the
colonic mucosa where it replicates in the cytosol of epithelial cells and spreads from cell to cell. This
dissemination process relies on cytosolic actin-based motility and formation of membrane protrusions that
project into adjacent cells. The resolution of these membrane protrusions leads to formation of double
membrane vacuoles (DMVs), from which the bacteria subsequently escape, thereby gaining access to the
cytosolic compartment of adjacent cells. Our lab has shown that the S. flexneri type three secretion system
(T3SS) is required at multiple stages of the dissemination process, including protrusion resolution and double
membrane DMV escape. I have shown recently that the T3SS effector protein IcsB contributes to S. flexneri
dissemination by promoting prompt and efficient escape from DMVs. Here, I propose to determine the
mechanism by which IcsB facilitates DMV escape (Aim 1) and its relevance to pathogenesis in our recently
developed infant rabbit model of human shigellosis (Aim 2). My central hypothesis is that IcsB is a critical
virulence factor that manipulates host Rho GTPases to promote prompt and efficient DMV escape. Since S.
flexneri dissemination is a critical determinant of pathogenesis, my work may reveal novel therapeutic
intervention for treating human shigellosis.

## Key facts

- **NIH application ID:** 10001964
- **Project number:** 5F31AI143139-02
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Erin A Weddle
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $34,187
- **Award type:** 5
- **Project period:** 2019-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001964

## Citation

> US National Institutes of Health, RePORTER application 10001964, Role of the T3SS  effector protein IcsB in Shigella flexneri infection (5F31AI143139-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10001964. Licensed CC0.

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