# Constitutive oxalate-biodegrading Bacillus subtilis for kidney stones

> **NIH NIH R43** · UNLOCKED LABS INC. · 2022 · $259,284

## Abstract

Project Summary / Abstract
 Kidney stones (nephrolithiasis) are an extremely painful and debilitating condition. About
12% of people will experience kidney stones in their lifetime, and about 70% of those will have
recurrences. The economic burden of kidney stones is estimated to exceed $5 billion per year
in the USA alone. Each year, over 3 million workdays are lost in the USA due to kidney stones.
75% of kidney stones consist of calcium oxalate (CaOx), and are caused by excessive urinary
oxalate levels.
 Unfortunately, current treatment options all have serious drawbacks. A low oxalate diet is
routinely recommended for CaOx stone patients, but is not very effective by itself. Alkalinizing
agents such as potassium citrate can reduce stone recurrence, but are costly and often cause
GI distress. Thiazide diuretics come with frequent, potentially life-threatening adverse effects
such as hypokalemia. Thus, there remains a strong need for the development of new kidney
stone treatment options that are both safe and effective.
 We propose to develop and test a new kidney stone treatment consisting of a novel
Bacillus subtilis strain that overexpresses endogenous oxalate biodegrading enzymes. As
bacteria stay in the gut, the spectrum of potential side effects is massively reduced as
compared to small molecule drugs. Thus, our innovative approach is designed to result in an
affordable, safe, and broadly effective kidney stone treatment option.
 In this Phase I SBIR project, we will develop new Bacillus subtilis strains engineered to
biodegrade oxalate. We will produce and test different strains to optimize oxalate
biodegradation capacity. As we will chromosomally overexpress endogenous enzymes in a
spore-forming bacterium, our approach avoids key drawbacks of previously developed oxalate-
degrading microbes. Finally, we will determine if the best performing engineered strain can
effectively reduce urine oxalate levels in a relevant rat model.

## Key facts

- **NIH application ID:** 10484663
- **Project number:** 1R43DK133067-01
- **Recipient organization:** UNLOCKED LABS INC.
- **Principal Investigator:** Christoph Geisler
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $259,284
- **Award type:** 1
- **Project period:** 2022-09-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10484663

## Citation

> US National Institutes of Health, RePORTER application 10484663, Constitutive oxalate-biodegrading Bacillus subtilis for kidney stones (1R43DK133067-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10484663. Licensed CC0.

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