# BLR&D Research Career Scientist Award Application

> **NIH VA IK6** · SOUTHERN ARIZONA VA HEALTH CARE SYSTEM · 2021 · —

## Abstract

Project Summary/Abstract
The overarching goal of our research is to understand the molecular basis of disease
caused by enteric bacterial pathogens, and to leverage this knowledge to develop
therapeutic agents that will benefit the Veteran population. A major focus of our
laboratory is the study of the bacterial pathogen, Clostridium difficile, which causes
healthcare-associated infections, and has been designated an “Urgent Threat” by the
Centers for Disease Control and Prevention. The risk factors for acquiring C. difficile
infection include age over 65 years, antibiotic treatment, and use of acid-suppressors; this
combination of risk factors makes Veterans especially vulnerable to infection.
Our ongoing epidemiological studies show that C. difficile infection rates in the Tucson
VA (and other Arizona) hospitals are above the national average, and that many patients
harbor `hyper-virulent' epidemic-associated strains of the pathogen. We have
characterized VA C. difficile strains in detail, uncovered novel virulence strategies
employed by these organisms, used cutting-edge genome analyses to track their evolution
and spread, and provided feedback to physicians in an effort to reduce incidence of
infections.
We have also made several innovative advances in exploring the molecular mechanisms
by which C. difficile causes disease. For these efforts, we have extensively used mass
spectrometry techniques to globally analyze various strains to discern their unique
virulence potential. Further, we have adopted, and greatly improved, recent
methodologies to genetically manipulate C. difficile in order to understand its virulence;
this has allowed us to knock out, or limit the expression of, various genes. Beyond the
pioneering work revealing that C. difficile toxins contribute to disease, we have uncovered
key roles for non-toxin factors including flagella, capsular polysaccharides and
superoxide reductase in virulence. We have also used mass spectrometry to understand
corresponding changes in host cells.
Finally, building on our understanding of how C. difficile attaches to the host intestine,
we recently designed and engineered a novel, safe “synthetic biologic” agent to express C.
difficile adhesins. In an animal model of infection, the agent was able to completely block
C. difficile infection and disease. This product, the first generation of which is fully
supported by our current VA Merit award, is now protected by a provisional patent, and
is currently under intensive further refinement. It is anticipated that the agent will be an
effective, safe, “first-in-kind” non-antibiotic option to prevent C. difficile infection in
Veterans, as well as all susceptible individuals.

## Key facts

- **NIH application ID:** 10265372
- **Project number:** 5IK6BX003789-05
- **Recipient organization:** SOUTHERN ARIZONA VA HEALTH CARE SYSTEM
- **Principal Investigator:** Gayatri Vedantam
- **Activity code:** IK6 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10265372

## Citation

> US National Institutes of Health, RePORTER application 10265372, BLR&D Research Career Scientist Award Application (5IK6BX003789-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10265372. Licensed CC0.

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