# Studies towards a pan-genome and genetic manipulation of Clostridium scindens

> **NIH NIH R03** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2020 · $75,223

## Abstract

Project Summary
Recent studies suggest that Clostridium scindens is protective against C. difficile infection in vivo. Antibiotic-
induced dysbiosis results in altered bile acid profile which is thought to allow C. difficile to grow and cause
infection. Prior studies have shown that host bile acids such as taurocholic acid induce C. difficile spore
germination in the GI tract; whereas conversion of host bile acids to secondary bile acids such as deoxycholic
acid (DCA) by C. scindens prevents C. difficile spore germination and vegetative cell growth. However, a genetic
system is currently lacking in C. scindens, representing a barrier to demonstrating causation with respect to DCA
formation and inhibition of C. difficile growth and virulence. We have a collection of over a dozen strains of C.
scindens strains whose genome sequences are not known. In Aim 1, we propose to sequence the complete
genomes of these strains. We have already completed the genome/methylome of C. scindens ATCC 35704T.
Determining the ‘pan-genome’ of C. scindens will allow determination of strain variation, and may allow
identification of strains more susceptible to genetic manipulation. We will also perform transcriptomic analysis
with two C. scindens strains in a newly developed defined medium and identify genes differentially expressed in
the presence of bile acids. In Aim 2 we test the hypothesis that the barrier to genetic manipulation of C. scindens
is restriction modification (FM) systems. Methylome data has identified extensive m6A modification among
conserved sequences in the genome. We will utilize a plasmid artificial modification (PAM) approach to
developing a pyrE counter-selectable marker. These studies will provide substantial progress in the
understanding of Clostridium scindens biology, bile acid metabolism, and significant progress towards genetic
manipulation of C. scindens. This will allow future proposals aimed at testing the hypothesis that DCA formation
by C. scindens protects against C. difficile infection in vivo.

## Key facts

- **NIH application ID:** 9979542
- **Project number:** 1R03AI147127-01A1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Jason Michael Ridlon
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $75,223
- **Award type:** 1
- **Project period:** 2020-02-24 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9979542

## Citation

> US National Institutes of Health, RePORTER application 9979542, Studies towards a pan-genome and genetic manipulation of Clostridium scindens (1R03AI147127-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9979542. Licensed CC0.

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