# Targeting antibiotic resistance genes in Vibrio cholerae using a phage-encoded CRISPR-Cas system to improve efficacy of phage prophylaxis

> **NIH NIH R21** · PHAGEPRO, INC. · 2022 · $204,527

## Abstract

PROJECT SUMMARY
The incessant rise of multidrug resistance in bacterial pathogens has created a dire situation that necessitates
development of new modalities for preventing and treating infectious diseases. Phage prophylaxis and phage
therapy represent one such approach, since phages are not affected by antibiotic resistance phenotypes. The
causative agent of cholera, Vibrio cholerae, has become extensively drug resistant (XDR) in just the past
decade due to indiscriminate and widespread antibiotic use in the community in low- and middle-income
countries. We recently reported a phage product, comprised of virulent phages ICP1, ICP2 and ICP3, that
effectively prevents cholera in animal models, which could be used to reduce infection rates those at-risk.
However, that work used an antibiotic-sensitive, pre-1980 strain of V. cholerae. Here, we seek to test two
hypotheses that, if substantiated, could dramatically improve phage prophylaxis for cholera and would lend
itself to improving phage products for other diseases caused by multidrug-resistant bacteria. The first
hypothesis is that incorporating CRISPR spacers into ICP1, which specifically target antibiotic resistance
genes in XDR V. cholerae, can improve the ability of ICP1 to kill these strains both in vitro and in animal
models, thereby better protecting the animals from infection. The second hypothesis is that by targeting
antibiotic resistance genes for cleavage by CRISPR-Cas, we can dramatically reduce their frequencies of
horizontal gene transfer.

## Key facts

- **NIH application ID:** 10320480
- **Project number:** 5R21AI156828-02
- **Recipient organization:** PHAGEPRO, INC.
- **Principal Investigator:** Andrew Camilli
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $204,527
- **Award type:** 5
- **Project period:** 2021-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10320480

## Citation

> US National Institutes of Health, RePORTER application 10320480, Targeting antibiotic resistance genes in Vibrio cholerae using a phage-encoded CRISPR-Cas system to improve efficacy of phage prophylaxis (5R21AI156828-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10320480. Licensed CC0.

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