# High Throughput Screen for Inhibitors of Shigella Flexneri Dissemination

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2020 · $627,361

## Abstract

Abstract
Shigella flexneri is the leading cause of bacillary dysentery (bloody diarrhea) with 165 million cases per year
worldwide, including 1 million deaths. There is no vaccine currently available and the isolation of multiple
antibiotic resistant strains from patients worldwide is becoming the norm. S. flexneri pathogenesis relies on the
colonization of the human colon where the pathogen invades epithelial cells and spreads directly from cell to
cell through actin-based motility. Using an infant rabbit model of human shigellosis recently developed by our
group, we have discovered that the severity of the symptoms observed during bacillary dysentery, including
bloody diarrhea and destruction of the intestinal mucosa, correlates with the efficiency of S. flexneri
dissemination through cell-to-cell spread. Targeting the cellular pathways supporting S. flexneri dissemination
therefore represents a potential medical countermeasure for bacillary dysentery. Here, we propose to discover
small molecules that inhibit S. flexneri dissemination (Aim 1) and to prioritize the hit set based on chemical and
biological triage (Aim 2) and limited and exploratory medicinal chemistry (Aim 3).

## Key facts

- **NIH application ID:** 10029698
- **Project number:** 1R01AI153455-01
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** HERVE F AGAISSE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $627,361
- **Award type:** 1
- **Project period:** 2020-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10029698

## Citation

> US National Institutes of Health, RePORTER application 10029698, High Throughput Screen for Inhibitors of Shigella Flexneri Dissemination (1R01AI153455-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10029698. Licensed CC0.

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