# sRNAs in EHEC virulence

> **NIH NIH R21** · UNIVERSITY OF VIRGINIA · 2021 · $237,471

## Abstract

PROJECT SUMMARY
 The ability of bacteria to rapidly sense and respond to changes in the environment is fundamental
to colonization and survival. This is especially relevant for gastrointestinal pathogens that must
effectively compete for nutrients with the microbiota as well as precisely coordinate gene expression
to establish infection. Small RNAs (sRNAs) are emerging as important factors that enable efficient
spatiotemporal expression of genes in response to the availability of a specific metabolite and/or
environmental cues, and thus play a central role in pathogenesis. The bacterial pathogen
enterohemorrhagic Escherichia coli O157:H7 (EHEC) colonizes the human colon and causes
hemorrhagic colitis and hemolytic uremic syndrome (HUS), which can be fatal. EHEC encodes
several important virulence factors, including the potent Shiga toxin that causes HUS and a type three
secretion system (T3SS) and effectors necessary for attaching and effacing (AE) lesion formation on
enterocytes. EHEC has a very low infectious dose, suggesting that EHEC has evolved mechanisms to
exploit nutrients in the host and precisely control virulence gene expression to occur within
appropriate host niches. Our studies underscore the importance of sRNAs in bacterial virulence by
demonstrating that two sRNAs, DicF and MavR, play important roles in modulating EHEC virulence.
DicF influences expression of the T3SS and is required for AE lesion formation. DicF also modulates
expression of genes encoding Shiga toxin, transcriptional regulators, and adhesins. MavR regulates
EHEC metabolism as well as stress responses and is essential for robust colonization of the
mammalian gastrointestinal tract. Moreover, our data indicate that these sRNAs regulate target gene
expression via unusual mechanisms. In this application, we will investigate the molecular mechanisms
of DicF- and MavR-dependent gene regulation and comprehensively identify direct targets of DicF
and MavR. The proposed studies will shed light not only on EHEC virulence but also on sRNA-
dependent regulatory mechanisms that may be important for gene regulation in diverse bacterial
pathogens.

## Key facts

- **NIH application ID:** 10286819
- **Project number:** 1R21AI163565-01
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Melissa Kendall
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $237,471
- **Award type:** 1
- **Project period:** 2021-05-20 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10286819

## Citation

> US National Institutes of Health, RePORTER application 10286819, sRNAs in EHEC virulence (1R21AI163565-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10286819. Licensed CC0.

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