# Sugar regulation of EHEC virulence

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $653,082

## Abstract

Project Summary/Abstract
The gastrointestinal (GI) tract is populated by a dense and diverse microbiota that impacts
human health. Although the microbiota composition at the species level for each individual is
unique as a fingerprint, its composition at the phyla level is more conserved. The predominant
phyla are Bacteroidetes and Firmicutes, followed by Proteobacteria. The gut microbiota has
been largely regarded as a resistance barrier towards enteric pathogens. However, the enteric
pathogens that cause infectious colitis, enterohemorrhagic E. coli (EHEC) O157:H7 and
Citrobacter rodentium (extensively used as a surrogate EHEC model for murine infections,
given that EHEC does not infect mice), exploit cues and nutrients made available by members
of the microbiota to regulate their virulence program. They sense several metabolites, including
sugar sources such as fucose, and organic acids such as succinate to gauge the GI
biogeography and precisely regulate their virulence programs. The EHEC Cra/KdpE/FusR
signaling cascade plays a crucial role in this regulation. The relationship between EHEC and
different members of the microbiota varies. Our studies using a representative member of each
of the main phyla, Bacteroides thetatiotaomicron (Bacteroidetes), Enterococcus faecalis
(Firmicutes) and commensal E. coli (Proteobacteria) suggest that EHEC virulence expression
varies in response to these commensals, as well as to different combinations of them. In this
grant proposal we aim to address how different minimal microbiota compositions impact enteric
infections. These studies will build from reductionist to holistic approaches to delve into
mechanistic aspects of pathogen-microbiota-host interactions. It is notable that these studies
will also be relevant to other enteric pathogens, such as Salmonella enterica and Clostridium
difficile, among others, which share several of these pathogen-microbiota interaction strategies
with EHEC. Hence the specific aims of this proposal are: Specific Aim 1. Investigate the impact
of different members of the microbiota in EHEC’s Cra/KdpE/FusR signaling cascade. Specific
Aim 2. Investigate the impact of different microbiota compositions on EHEC infection of
enteroids. Specific Aim 3. Investigate the impact of different microbiotas in C. rodentium murine
infections.

## Key facts

- **NIH application ID:** 10065360
- **Project number:** 1R01AI154597-01
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** ANTHONY W MARESSO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $653,082
- **Award type:** 1
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10065360

## Citation

> US National Institutes of Health, RePORTER application 10065360, Sugar regulation of EHEC virulence (1R01AI154597-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10065360. Licensed CC0.

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