# Characterization of a novel family of Small Regulatory Proteins modulating virulence in Enterobacteriaceae

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2022 · $403,750

## Abstract

PROJECT SUMMARY/ABSTRACT
In the United States, the Center for Disease Control and Prevention (CDC) has estimated that more than 200
million episodes of acute gastroenteritis occur annually, resulting in nearly 1 million hospitalizations and over
5000 deceases. Vaccines against enteric pathogens are not available due, in part, to limited knowledge of the
many virulence mechanisms that enteropathogens have evolved to colonize, multiply and escape host
defenses. We have recently discovered the ANR (AraC Negative Regulators) family, comprising a large
number of small regulatory proteins produced by diverse clinically important enteric pathogens including Vibrio
spp., Salmonella spp., Shigella spp., Yersinia spp., Citrobacter spp., enterotoxigenic (ETEC), enteropathogenic
EPEC, enterohaemorragic (EHEC) and enteroaggregative E. coli (EAEC). Members of the ANR family
modulate the expression of virulence factors such as fimbriae, toxins, type-3 and type-6 secretion systems,
and genes associated with metabolism, stress-response and fitness, by protein-protein interactions with
positive transcriptional regulators of the AraC/XylS family and negative regulators of the HNS family.
Furthermore, the absence of this regulatory system affects bacterial pathogenesis in a natural model of
infection. Our overall hypothesis is that the ANR family plays a critical role in the concerted regulation of fitness
and virulence in pathogens of the Enterobacteriaceae family by taking concomitant control of AraC and HNS
global regulators. Here, we propose to obtain mechanistic insights into ANR molecular interactions (AIM-1),
regulation (AIM 2) and pathogenesis (AIM-3) using EAEC, EPEC and C. rodentium as pathogen models,
human stem cell technology and a natural animal model of disease, coupled with genetic, biochemical and
molecular approaches such as Surface Plasmon Resonance (SPR), Time-lapse fluorescence microscopy
(TLFM) and ChIP-seq. Our proposed studies will advance our knowledge of global gene regulatory
mechanisms that govern fitness and virulence in pathogenic bacteria, and will likely open new avenues for
therapeutic intervention.

## Key facts

- **NIH application ID:** 10445732
- **Project number:** 1R01AI162858-01A1
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Araceli Elvira Santiago
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $403,750
- **Award type:** 1
- **Project period:** 2022-02-02 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10445732

## Citation

> US National Institutes of Health, RePORTER application 10445732, Characterization of a novel family of Small Regulatory Proteins modulating virulence in Enterobacteriaceae (1R01AI162858-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10445732. Licensed CC0.

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