# Identification of Bacterial Genes that Disrupt Host Proteostasis

> **NIH NIH R03** · UNIVERSITY OF FLORIDA · 2020 · $74,565

## Abstract

Protein conformational diseases (PCDs) are characterized by a progressive loss of neuronal or muscle
function due to protein misfolding and aggregation, a common feature among diseases such as Alzheimer's,
Parkinson's, Huntington's, or Lou Gehrig's disease. The exact factors that influence PCDs are not known. Recent
evidence suggests that bacteria may contribute to the pathogenesis of these neurodegenerative diseases. To
better understand the influence of bacteria on protein homeostasis (proteostasis), we are studying the effect of
bacterial colonization of the Caenorhabditis elegans gut on protein aggregation in the intestine and other tissues.
In a screen of 52 of the most common human pathogenic-commensal bacteria, we found two Gram-negative
species, Pseudomonas aeruginosa and Klebsiella pneumoniae, that enhanced protein aggregation in the
intestine by nearly five-fold; these two strains also affect protein aggregation in the muscle. Both species are
part of the normal human microbiome and are known opportunistic pathogens. An increase in the abundance of
these bacteria within the human gut was previously linked with the enhanced progression of neurodegenerative
diseases. Collectively, these results suggest that intestinal bacteria affect the host folding environment; however,
which bacterial factors are responsible for the enhancement of aggregation remains unknown. As such, we
propose to screen genome-wide mutant libraries of P. aeruginosa and K. pneumoniae for genes that will abolish
the enhancement of protein aggregation upon colonization of the C. elegans intestine. Identification of bacterial
genes and pathways that are responsible for disruption of host proteostasis will provide a new mechanistic
understanding of host-bacteria interaction that can provide a basis for the development of prophylactics,
therapeutics, and biomarkers for PCDs.

## Key facts

- **NIH application ID:** 10041813
- **Project number:** 1R03AG069056-01
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Daniel Milosz Czyz
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $74,565
- **Award type:** 1
- **Project period:** 2020-08-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10041813

## Citation

> US National Institutes of Health, RePORTER application 10041813, Identification of Bacterial Genes that Disrupt Host Proteostasis (1R03AG069056-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10041813. Licensed CC0.

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