# Pathogenic Mechanisms of Bacillus Endophthalmitis

> **NIH NIH R01** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2020 · $358,109

## Abstract

PROJECT SUMMARY / ABSTRACT
 Intraocular bacterial infections (endophthalmitis) cause a significant number of cases of blindness
worldwide. Efforts to prevent damage to delicate ocular tissues during infection rely on swift and proper use of
therapeutics to rapidly kill organisms and arrest potentially damaging inflammation. Currently-used antibiotics
can kill organisms, but the effectiveness of anti-inflammatory drugs is controversial. No current therapies
neutralize toxins which damage nonregenerative tissues in the eye. Our overarching goal is to develop
more effective therapeutics which target and inhibit these events, preserving vision.
 Bacillus cereus (Bc) causes one of the most inflammatory and rapidly blinding forms of
endophthalmitis. This common environmental organism enters the eye during trauma or bloodstream
infection, and is also a reported surgical contaminant. Eyes infected with Bc can be rendered sightless in a
short period of time, so effective treatment is critical to saving vision. This proposal focuses on mechanisms
related to the organism and its behavior in the eye, and highlights events during the infection course prior to
significant retinal damage and inflammation—a time when therapeutic intervention would be most valuable. We
propose four aims that address Bc pathogenesis during important early events in endophthalmitis:
 Aim 1 will analyze elements of the intraocular environment that trigger germination of Bc spores. The
 mechanisms involved in transformation from spore to vegetative state in the eye will be examined.
 Aim 2 will further explore innate immune pathway recognition of potential Bc agonists. For TLR2, we will
 address the role of peptidoglycan deacetylation and teichoic acid as agonists. For TLR4, we will address
 the role of cereolysin and heat-labile surface components as agonists.
 Aim 3 will examine whether intraocular inflammation prompts migration of Bc throughout the eye.
 RNASeq data suggest that flagellar and motility systems of Bc are highly expressed in vivo.
 Aim 4 will test the hypothesis that during inflammation, products secreted by Bc disarm infiltrating
 neutrophils. Candidates include superoxide dismutase, immune inhibitor A, and cereolysin, and mutants
 deficient in each will be tested for potential anti-neutrophil activity.
These independent but related aims are a logical extension of our ongoing research into the pathogenic
mechanisms underlying bacterial endophthalmitis. For Bc endophthalmitis patients, ineffective treatment
often results in significant vision loss or loss of the globe itself. Therefore, identifying factors and
pathways important to early disease events disease is critical to developing novel and effective therapeutic
options for this blinding infection.

## Key facts

- **NIH application ID:** 9965962
- **Project number:** 5R01EY028810-03
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** Michelle C Callegan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $358,109
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9965962

## Citation

> US National Institutes of Health, RePORTER application 9965962, Pathogenic Mechanisms of Bacillus Endophthalmitis (5R01EY028810-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9965962. Licensed CC0.

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