# EptB pseudogene formation as a novel mechanism of typhoidal Salmonella virulence

> **NIH NIH F30** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $50,520

## Abstract

PROJECT SUMMARY
 Salmonella enterica is a highly diverse species of Gram-negative bacteria that can be
grouped into typhoidal and non-typhoidal serovars. Non-typhoidal serovars, such as S.
Typhimurium, cause gastroenteritis and inflammatory diarrhea, whereas typhoidal serovars,
such as S. Typhi, cause typhoid fever, a systemic disease with a comparatively decreased
inflammatory response. However, the virulence strategies that set typhoidal Salmonella
serovars apart from non-typhoidal Salmonella serovars remain understudied. Experiments
proposed in this application are aimed at addressing this important gap in knowledge. Our long-
range goal is to elucidate the molecular mechanisms by which typhoidal Salmonella serotypes
manipulate host responses during infection. Previously, comparative analysis of Salmonella
genomes revealed that typhoidal serovars contain a higher number of pseudogenes than non-
typhoidal serovars, suggesting that pseudogene accumulation may contribute to the differences
in disease manifestation caused by these serovars. One such pseudogene in S. Typhi is eptB,
which encodes a phosphoethanolamine transferase that specifically modifies the outer keto-
deoxyoctulosonate (KDO) residue of lipopolysaccharide (LPS). Our central hypothesis is that
eptB pseudogene formation in S. Typhi represents a novel virulence mechanism that
contributes to the stealth and immune evasion properties that characterize typhoidal Salmonella
serovars. The objectives of this application are to identify the mechanism by which eptB
pseudogene formation moderates the host immune response and to determine how acquisition
of the eptB pseudogene synergizes with accumulation of additional pseudogenes to promote
the virulence of typhoidal Salmonella serovars. To test our hypothesis and accomplish these
objectives, we will examine how eptB pseudogene formation impacts binding of the host protein,
intelectin, to LPS to regulate host responses to LPS (specific aim 1) and also determine how
eptB pseudogene formation offsets the acquisition of other typhoidal pseudogenes to enhance
Peyer's patch colonization (specific aim 2). Our analysis of this novel virulence mechanism in
typhoidal Salmonella serovars will be useful and necessary to understand how the interplay
between pathogen and the innate immune system gives rise to responses that distinguish
typhoid fever from gastroenteritis, thereby ushering in a significant conceptual advance.

## Key facts

- **NIH application ID:** 9842803
- **Project number:** 5F30AI136309-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Lillian Zhang
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,520
- **Award type:** 5
- **Project period:** 2018-01-15 → 2021-10-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9842803

## Citation

> US National Institutes of Health, RePORTER application 9842803, EptB pseudogene formation as a novel mechanism of typhoidal Salmonella virulence (5F30AI136309-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9842803. Licensed CC0.

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