# Significance of Corneal Cell Invasion by Bacteria

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2022 · $389,213

## Abstract

Summary:
P. aeruginosa is a leading cause of blinding eye disease. Contributing to disease pathogenesis is invasion of
corneal epithelial cells, as we have demonstrated in vitro and in vivo. Here, we report that P. aeruginosa can
establish multiple niches inside corneal epithelial cells, some colonizing the cytoplasm and other vacuoles – often
in the same cell. Reporter expression results show different phenotypic states in these alternate locations, the
pattern suggesting “acute” infection mode for cytoplasmic bacteria and “chronic” (biofilm forming) mode for
those in vacuoles. While genetic regulation of the switch between these two states has been extensively studied
in vitro, how this might work inside a cell is unknown. Our published and preliminary data show that “acute”
and “chronic” modes cooperate to determine corneal epithelial cell responses, to allow P. aeruginosa to penetrate
the multilayered corneal epithelium, to colonize the cornea, and to cause pathology. Here, we will test the
hypothesis that their unique intracellular niches contribute to their cooperative efforts during corneal infection.
The three aims will explore significance of intracellular diversification to the bacteria, to the host corneal
epithelial cell, and to disease pathogenesis. Approaches will utilize multiple novel tools developed using funding
from this grant, including bacterial constructs, imaging technologies, and infection models. The two consultants
are leading experts in bacterial gene regulation, respectively covering both phenotypes. Importantly, our data
suggest that vacuolar P. aeruginosa transition into biofilms, which can be difficult to kill or even to culture. A
vacuole would enclose a biofilm inside two host membranes - vacuolar and plasma. This intracellular phenotype
alone could explain why P. aeruginosa infections are notoriously difficult to manage and why disease can
continue despite apparent sterilization of the ulcer.

## Key facts

- **NIH application ID:** 10426294
- **Project number:** 5R01EY011221-24
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Suzanne MJ FLEISZIG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $389,213
- **Award type:** 5
- **Project period:** 1995-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10426294

## Citation

> US National Institutes of Health, RePORTER application 10426294, Significance of Corneal Cell Invasion by Bacteria (5R01EY011221-24). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10426294. Licensed CC0.

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