# Probing the role of commensal intestinal fungi during Salmonella pathogenesis

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2022 · $392,077

## Abstract

PROJECT SUMMARY
Despite modern sanitation and hygiene, gastrointestinal infections continue to be a significant health problem in
the United States and represent a tremendous economic burden in terms of loss of work. One of the crucial
steps of Salmonella pathogenicity is the establishment of colonization in the gut. While the host eventually clears
the infection with Salmonella, initial host responses benefit the growth of Salmonella. Similarly, also some
commensal bacteria promote Salmonella intestinal colonization. These resident bacteria liberate for example
otherwise inaccessible carbon sources. However, previous studies focused exclusively on the role of commensal
bacteria during Salmonella pathogenesis and did not address the role of another important group of
microorganisms that resides in the gut: commensal intestinal fungi. In recent years, this under-studied
component of the microbiota has been implicated in a variety of diseases including Inflammatory Bowel Disease.
However, the role of commensal fungi during pathogenesis of gut pathogens like Salmonella is unknown.
This is despite the fact that Salmonella encodes genes that make an interaction with commensal gut fungi highly
likely. In this regard, Salmonella produces three receptors for fungal and bacterial siderophores (so-called
xenosiderophores). Siderophores are small molecules that are secreted by fungi and bacteria for iron acquisition
in low iron environments like the inflamed gut. Our preliminary data show that expression of two fungal
siderophore receptors confers a growth advantage to Salmonella in conventionally raised but not in germ-free
mice. Furthermore, chitinases produced by Salmonella could weaken the chitin-containing fungal cell wall to
enable Salmonella to acquire fungal nutrients including intracellularly stored siderophores. We therefore
hypothesize that Salmonella acquires xenosiderophores and accesses fungal nutrients with the help of
chitinases to increase colonization in the gut. We plan to investigate in Aim 1 how fungal xenosiderophores
promote Salmonella colonization in the gastrointestinal tract by depletion or addition of fungi. We will sequence
the fungal microbiota to identify siderophore-producing fungi. We will also determine the growth promoting effect
of the third xenosiderophore receptor, which binds a bacterial siderophore. In Aim 2, we propose to study how
members of the microbiota compete with Salmonella for xenosiderophores. For this, we will reduce the
complexity of the microbiota. Germ-free mice allow for specific colonization with producers and competitors for
fungal siderophores. We will test if common fungal and bacterial commensals that do not produce siderophores
like Candida, Saccharomyces, and Bacteroides compete with Salmonella for xenosiderophores. In Aim 3, we
will elucidate if Salmonella chitinases enhance Salmonella pathogenicity. We will test two different functions of
chitinases: weakening the fungal cell wall to access fung...

## Key facts

- **NIH application ID:** 10321587
- **Project number:** 5R01AI143641-04
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Judith Behnsen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $392,077
- **Award type:** 5
- **Project period:** 2019-01-16 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10321587

## Citation

> US National Institutes of Health, RePORTER application 10321587, Probing the role of commensal intestinal fungi during Salmonella pathogenesis (5R01AI143641-04). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10321587. Licensed CC0.

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