# Modulation of host immunity with recombinant peptidoglycan hydrolases

> **NIH NIH R21** · SCRIPPS RESEARCH INSTITUTE, THE · 2024 · $506,000

## Abstract

PROJECT SUMMARY
There exist few preventive or therapeutic modalities for vulnerable hosts against bacterial diarrheal illness.
Further, the limited effectiveness of anti-infectives is being compromised by the antimicrobial resistant crisis. In
response to this situation, physicians and scientists have investigated the role of probiotics. Despite promising
preliminary data showing benefit in weakened immune hosts and against drug-resistant isolates, probiotic clinical
trials have demonstrated inconsistent therapeutic and safety profiles. For these reasons, identifying the
molecular mechanisms by which probiotics provide benefit is needed to develop new therapeutics. Notably, the
Hang laboratory has discovered specific Enterococcus peptidoglycan hydrolases can improve intestinal barrier
function and confer resistance against enteric infections in mouse models. Furthermore, these peptidoglycan
hydrolases genetically engineered into Lactobacillus species were able to recapitulate protective effects. Given
the unclear efficacy of probiotics in humans, we aim to develop orally available recombinant peptidoglycan
hydrolases therapeutics that will promote intestinal barrier function to protect against enteric pathogens. We
therefore propose to evaluate the activity of recombinant Enterococcus peptidoglycan hydrolase hydrogel
formulations in mouse models of enteric infection (Aim 1) as well as explore peptidoglycan remodeling enzymes
from other microbiota species/strains (Aim 2). The work proposed herein should afford new preventive and
treatment modalities for vulnerable hosts against enteric infections.

## Key facts

- **NIH application ID:** 10952837
- **Project number:** 1R21AT012958-01
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Howard C Hang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $506,000
- **Award type:** 1
- **Project period:** 2024-09-13 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10952837

## Citation

> US National Institutes of Health, RePORTER application 10952837, Modulation of host immunity with recombinant peptidoglycan hydrolases (1R21AT012958-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10952837. Licensed CC0.

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