# Metagenomic discovery and optimization of novel endolysins targeting Gardnerella vaginalis to treat bacterial vaginosis

> **NIH NIH R43** · TOPAZ BIOSCIENCES, INC. · 2024 · $300,000

## Abstract

PROJECT SUMMARY
Bacterial vaginosis (BV) is the most common vaginal dysbiosis in women of reproductive age and is associated
with a number of serious health complications. Gardnerella vaginalis is believed to play a critical role in the
etiology of BV, functioning as a pioneering organism that can displace beneficial lactobacilli and initiate BV
biofilm development. As G. vaginalis proliferates, the pH of the vaginal environment increases, leading to
further decreases in lactobacilli and enabling the growth of additional BV-associated bacteria within these
biofilms. Standard antibiotic treatment for BV suffers from high relapse rates, the development of antibiotic
resistant bacteria, and collateral damage to the healthy lactobacilli in the vaginal microbiome. Given these
drawbacks, novel antimicrobial agents that can provide alternatives to antibiotics and can selectively
target BV-associated bacteria without damaging beneficial bacteria are urgently needed.
Endolysins are phage-encoded enzymes that can degrade bacterial cell walls. Exogenously added endolysins
can quickly lyse their target bacteria and because they bind very specific epitopes in target cell walls, they can
have lytic specificity down to a single species or even sub-species. Given these properties, endolysins hold
enormous potential as high-specificity microbiome modulators. Recently, endolysins targeting G. vaginalis
have been identified and demonstrated to kill G. vaginalis. However, the endolysins that have been
characterized thus far are not well suited for commercial development. Endolysins that are more active, more
thermostable, and function at lower pH are needed to be broadly useful for treating BV.
At Topaz Biosciences, we have developed a proprietary metagenomic platform for the discovery and
optimization of endolysins. We have previously leveraged this platform to develop endolysins against
Staphylococcus aureus that are more active, more thermostable, and have a broader pH range than
benchmark enzymes. In this Phase I proposal, we will leverage this platform to expand the diversity of
endolysins known to have activity against G. vaginalis and then exploit this diversity to develop
chimeric enzymes with improved properties. To accomplish this, we will take advantage of the modularity of
endolysins to build a library of endolysin “parts” – enzymatic domains (EADs) and cell wall binding domains
(CBDs) that we will systemically characterize for anti-Gardnerella activity, thermostability, pH tolerance, biofilm
reduction, and genus specificity. These parts will be sourced both from recently identified endolysins from
Gardnerella prophages as well from diverse endolysins/domains from proprietary and public metagenomic
databases that we predict to have anti-Gardnerella activity. Finally, we will leverage sequence-function insights
gained from our “parts” development to design chimeric endolysins composed of EADs and CBDs with the
most promising properties to generate enzymes...

## Key facts

- **NIH application ID:** 11005378
- **Project number:** 1R43AI186717-01
- **Recipient organization:** TOPAZ BIOSCIENCES, INC.
- **Principal Investigator:** Oliver Wei Liu
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $300,000
- **Award type:** 1
- **Project period:** 2024-07-08 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11005378

## Citation

> US National Institutes of Health, RePORTER application 11005378, Metagenomic discovery and optimization of novel endolysins targeting Gardnerella vaginalis to treat bacterial vaginosis (1R43AI186717-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11005378. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*