# Role of DeoR-family transcription regulators in metabolic adaptation of Listeria monocytogenes to stressful food-related environmental conditions and intracellular host cells

> **NIH NIH P20** · MISSISSIPPI STATE UNIVERSITY · 2021 · $284,664

## Abstract

Project Summary
Listeria monocytogenes (LM) is a very dangerous foodborne pathogen with a high mortality rate (20 - 30%). A
major reason why LM is dangerous is because it can survive in a variety of environmental stresses
encountered during its infection cycle, including low pH, high salt, low temperature, and the intracellular
environments. The ability of LM to survive in different environmental stresses is directly related to its ability to
adjust its metabolism depending on the type of stress and nutrient availability. There is a knowledge gap in our
understanding of the regulatory mechanisms controlling LM metabolic adaptations to stressful environmental
conditions. We have evidence that DeoR-family regulators serve this critical function by regulating LM
metabolism. Members of the DeoR-family regulators often serve as transcriptional repressors or activators in
sugar metabolism. By analyzing the genome of LM strain F2365, we found seven members of the DeoR-family
regulators. We constructed a LM deletion strain by targeting FruR-encoding DeoR-family regulator
(LMOf2365_2307). We found that F2365ΔfruR is attenuated and has decreased growth in macrophages
relative to the virulent parent strain F2365. Furthermore, deletion of fruR causes strong upregulation of
phosphofructokinase (fruK) and fructose-specific PTS system transporter subunit IIABC (fruA). Our central
hypothesis is that the DeoR-family transcriptional regulators contribute to the ability of LM to adapt to
environmental changes and replicate in host cells by acting as global regulators for many metabolic genes,
including phosphotransferase transport system (PTS) and ABC transporters. The specific goal of this proposal
is to determine the contribution of DeoR-family regulators to LM adaptation to harsh environmental conditions.
This goal will be achieved by performing the following two specific aims: Aim 1 elucidate the role of FruR in L.
monocytogenes intracellular replication. In this aim, we will analyze the glucose incorporation and metabolism
in F2365ΔfruR replicating in macrophage by 13C-perturbation techniques. We will compare the transcriptome of
parent and F2365ΔfruR strain during growth in macrophage cell line. We will determine whether the
intracellular growth defect of F2365ΔfruR is due to delayed vacuolar escape or due to a defect in the
hemolysin production.; Aim 2 define the role of other DeoR-family regulators in Listeria's response to stressful
conditions. This aim will determine the effect of DeoR-family genes in virulence and in growth defect in
macrophages cell lines. We will also identify the role of DeoR-family regulators in LM adaptation to food related
stress conditions, including exposure to acid and high salt. The rationale for this project is to determine
mechanisms that allow LM to tolerate and grow within stressful food-related environmental conditions and
survive in intracellular host cells, which will assist in the development of intervention strategies ...

## Key facts

- **NIH application ID:** 10261568
- **Project number:** 5P20GM103646-09
- **Recipient organization:** MISSISSIPPI STATE UNIVERSITY
- **Principal Investigator:** Hossam A Abdelhamed
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $284,664
- **Award type:** 5
- **Project period:** 2013-09-30 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10261568

## Citation

> US National Institutes of Health, RePORTER application 10261568, Role of DeoR-family transcription regulators in metabolic adaptation of Listeria monocytogenes to stressful food-related environmental conditions and intracellular host cells (5P20GM103646-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10261568. Licensed CC0.

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