# Impact of Flagellin Variants and Receptors on the Progression and Outcome of Sepsis

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2021 · $381,297

## Abstract

PROJECT SUMMARY
 Sepsis is a life-threatening systemic inflammatory condition that is initiated by the presence
of microorganisms in the bloodstream or tissues. During sepsis, the generation of excessive
inflammatory mediators, including cytokines and reactive oxygen species, can result in vascular
leakage, disseminated intravascular coagulation, and organ failure. In the United States, sepsis
kills over a quarter of a million people each year and is associated with extremely high health
care costs. Clinically, sepsis patients can have variable, often non-specific signs and symptoms
that make it difficult to accurately assess disease severity or predict outcomes. This variability is
frequently attributed to differences in the genetic background and immune status of individual
hosts. However, the nature of the infecting microbes can also impact disease severity. Strains of
Extraintestinal Pathogenic Escherichia coli (ExPEC) are the principal cause of bloodstream
infections and a leading cause of sepsis. Similarly lethal ExPEC isolates can trigger markedly
different host responses, irrespective of host background characteristics. These variances
correlate with differential stimulation of Toll-Like Receptor 5 (TLR5) by discrete flagellar
serotypes. Here we propose to 1) determine if flagellin variants influence the severity and
outcomes of sepsis, 2) establish how flagellin variants trigger differential host responses, and 3)
define roles for flagellin receptors in relevant models of sepsis. These studies will consider both
sex and age as variables, with an emphasis on ExPEC-induced sepsis in children and
neonates. By the end of this study we will have a clear mechanistic understanding of the effects
that flagellin variants and TLR5 have on ExPEC-induced sepsis. This work will challenge
prevailing views of what can drive variability in the signs and symptoms of sepsis and will
consequently aid the development of improved diagnostic tools and therapeutics.

## Key facts

- **NIH application ID:** 10136035
- **Project number:** 5R01GM134331-03
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** MATTHEW A MULVEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $381,297
- **Award type:** 5
- **Project period:** 2019-08-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10136035

## Citation

> US National Institutes of Health, RePORTER application 10136035, Impact of Flagellin Variants and Receptors on the Progression and Outcome of Sepsis (5R01GM134331-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10136035. Licensed CC0.

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