# BLRD Research Career Scientist Award Application

> **NIH VA IK6** · VA EASTERN COLORADO HEALTH CARE SYSTEM · 2022 · —

## Abstract

Salmonella infections are responsible for an estimated 3 million annual deaths worldwide. Multidrug
resistance among clinical Salmonella more than doubled from 2011 to 2013. The World Health
Organization has ranked Salmonella as one of the top 12 antibiotic resistant bacterial threats to global
health. The goal of this Research Career Scientist Award is to continue with our efforts to apply our
knowledge of Salmonella virulence to the development of novel antibiotics against multidrug resistant
bacterial pathogens.
Resistance of Salmonella and other pathogenic bacteria to antibiotics is in great part regulated by the
nucleotide alarmone guanosine tetraphosphate and the DksA protein. Both of these mediators bind to
the secondary channel of RNA polymerase, regulating transcription of central metabolic pathways and
a variety of virulence programs. We will carry on our research on the molecular mechanisms by which
guanosine tetraphosphate and DksA regulate Salmonella transcriptional programs. The Research
Career Scientist Award will also allow us to develop novel antibiotics that inhibit DksA-dependent
bacterial transcription. Binding of DksA to the secondary channel of RNA polymerase is in competition
with Gre transcription elongation factors. We have found that Gre proteins are needed for Salmonella
virulence and the resistance of this Gram-negative rod to antibiotics. We plan to characterize the
molecular mechanisms by which Gre factors promote bacterial pathogenesis and antibiotic resistance.
These research projects are highly collaborative in nature, involving scientific interactions with
investigators at the Veterans Affairs Eastern Colorado Healthcare System, the Atlanta VA Medical
Center and the Veterans Administration Ann Arbor Healthcare System. I plan to continue fostering
these productive collaborations. Training of junior faculty, graduate students and postdoctoral fellows
are also important components of this Research Career Scientist Award. Moreover, in collaboration
with other investigators at the at the Veterans Affairs Eastern Colorado Healthcare System and
Wisconsin-Madison VA Medical Center, we will continue mentoring promising CDA- 2 candidates, and
thus help train the next generation of outstanding VA scientists.

## Key facts

- **NIH application ID:** 10337064
- **Project number:** 5IK6BX005384-02
- **Recipient organization:** VA EASTERN COLORADO HEALTH CARE SYSTEM
- **Principal Investigator:** Andres Vazquez-Torres
- **Activity code:** IK6 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2020-10-01 → 2025-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10337064

## Citation

> US National Institutes of Health, RePORTER application 10337064, BLRD Research Career Scientist Award Application (5IK6BX005384-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10337064. Licensed CC0.

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