# Targeting NuoD for the treatment of H. pylori

> **NIH NIH R01** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2024 · $844,980

## Abstract

This proposal aims to develop novel, more effective, and selective therapies for the treatment of Helicobacter
pylori infections. Chronic infection with H. pylori causes peptic ulcers and gastric cancer. H. pylori is an
important drug-resistant pathogen, which is categorized as a high-priority pathogen by the WHO. Standard
therapy consists of a proton pump inhibitor (PPI) and two broad-spectrum antibiotics, usually clarithromycin
with either metronidazole or amoxicillin. These combinations are becoming increasingly ineffective with high
resistance rates, and substantially disrupt the gut's healthy microbiome. There is a considerable unmet need
for novel, more effective, and selective antibiotics to eradicate H. pylori. In our preliminary studies, we identified
the NuoD interface of Complex I as a druggable target for H. pylori. Respiration through Complex I is essential
for H. pylori, but not for most other bacteria, offering mechanistic selectivity and minimizing disruption of the
microbiome. We developed and validated a virtual screening platform for this target to identify leads with
improved pharmacological properties using the initial inhibitors. The virtual screen identifed hits that are
synthetically tractable with demonstrated on-target antibacterial activity, and both ex vivo and in vivo efficacy
against H. pylori. The ultimate aim of the proposal is to obtain carefully validated, narrow spectrum, orally
bioavailable, and efficacious NuoD inhibitors that will form the basis of a subsequent preclinical antibiotic
development effort. These studies will also provide a deeper understanding of H. pylori respiration and the
development of selective antibiotics against H. pylori.

## Key facts

- **NIH application ID:** 10834225
- **Project number:** 5R01AI170765-02
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** Michael LaFleur
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $844,980
- **Award type:** 5
- **Project period:** 2023-05-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10834225

## Citation

> US National Institutes of Health, RePORTER application 10834225, Targeting NuoD for the treatment of H. pylori (5R01AI170765-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10834225. Licensed CC0.

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