# Development of Faux-Biotics to combat the spread of hospital-acquired antibiotic-resistant infections

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2022 · $69,802

## Abstract

Project Summary
The CDC considers the escalation of antibiotic resistance to be one of the biggest public health concerns of
our time. Antibiotic resistance is a major issue both human and animal health, and resistant infections and
resistance genes can be transmitted between animals and the humans who interact with them. One of the
most urgent threats is Carbapenem-resistant Enterobacteriaceae (CRE). Antibiotic usage is a major risk factor
for the development of fecal CRE carriage, which is both a source of bloodstream infection and spread to other
susceptible patients through contact with hospital workers. Due to the lack of treatment options, these
infections can be deadly in up to 50% of patients who acquire them. Current therapies to restore colonization
resistance target the microbiota using fecal microbiota transplantation, prebiotics, or probiotics. However, for
patients who must remain on antibiotics, these treatment options are unlikely to be successful. A healthy
microbiota provides colonization resistance in two ways: by occupying all available niches in the intestine to
directly prevent other microbiota from colonizing, and through modification of the intestinal environment to
make it less welcoming for invading bacteria. The latter includes production of substances such as short-chain
fatty acids, which allow the microbiota to interact with host cells and improve intestinal health and colonization
resistance. The objective of this application is to devise a treatment to restore colonization resistance during
antibiotic therapy that exploit the pathways used by the microbiota under homeostatic conditions. Our
hypothesis is that 5-ASA, a drug that activates pathways in colonocytes used by the microbiota, will be
successful at restoring colonization resistance against carbapenem resistance Enterobacteriaceae after
antibiotic treatment in immunocompetent and immunocompromised hosts. To test our hypothesis, we will first
use an SPF mouse model of antibiotic administration and CRE exposure with or without treatment with 5-ASA.
Mice will be placed on a 5-ASA-containing diet either prior to CRE exposure (prevention) or after CRE infection
(treatment) and colonization will be monitored through feces and cecal contents. We will then infect Germ-free
mice recolonized with paired patient fecal samples collected before antibiotics are started and 4-7 days after
antibiotic therapy is initiated. These mice will also be placed on a 5-ASA-containing diet to demonstrate that
effective prevention or reduction of CRE colonization can be achieved in diverse patient microbiotas with
various antibiotic therapies. Finally, we will utilize a cyclophosphamide model of immunosuppression in mice to
demonstrate reduced CRE bacteremia as a result of 5-ASA-mediated reduction of intestinal CRE CFU.
Successful completion of the proposed research will provide pre-clinical evidence that 5-ASA, a clinically
approved drug, can be used to strengthen colonization resista...

## Key facts

- **NIH application ID:** 10515629
- **Project number:** 5F32AI161850-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Hannah P Savage
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $69,802
- **Award type:** 5
- **Project period:** 2021-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10515629

## Citation

> US National Institutes of Health, RePORTER application 10515629, Development of Faux-Biotics to combat the spread of hospital-acquired antibiotic-resistant infections (5F32AI161850-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10515629. Licensed CC0.

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