Inhibiting the Initiation of Clostridium difficile Spore Germination using Analogs of Chenodeoxycholic Acid, a Bile Acid

Sorg, Joseph A.; Sonenshein, Abraham L.

doi:10.1128/jb.00610-10

Cited by 332Clostridium difficile and Clostridium perfringens researchGut microbiota and healthBacterial Identification and Susceptibility Testing

Inhibiting the Initiation of Clostridium difficile Spore Germination using Analogs of Chenodeoxycholic Acid, a Bile Acid

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Sorg, Joseph A., Sonenshein, Abraham L.·2010·Journal of Bacteriology

DOI 10.1128/jb.00610-10PMC PMC2944524

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Abstract

To cause disease, Clostridium difficile spores must germinate in the host gastrointestinal tract. Germination is initiated upon exposure to glycine and certain bile acids, e.g., taurocholate. Chenodeoxycholate, another bile acid, inhibits taurocholate-mediated germination. By applying Michaelis-Menten kinetic analysis to C. difficile spore germination, we found that chenodeoxycholate is a competitive inhibitor of taurocholate-mediated germination and appears to interact with the spores with greater apparent affinity than does taurocholate. We also report that several analogs of chenodeoxycholate are even more effective inhibitors. Some of these compounds resist 7α-dehydroxylation by Clostridium scindens , a core member of the normal human colonic microbiota, suggesting that they are more stable than chenodeoxycholate in the colonic environment.

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Secondary bile acids can inhibit vegetative C. difficile growth.
“These secondary bile acids can inhibit vegetative C. difficile growth [53–55].”
From Role of the gut microbiota in nutrient competition and protection against intestinal pathogen colonization (2023) · cites this paper as [54]
A healthy gut microbiota promotes colonization resistance against C. difficile through metabolism of bile acids to both reduce primary bile acids, which promote C. difficile spore germination, and increase secondary bile acids, which inhibit C. difficile vegetative growth.
“Therefore, a healthy gut microbiota promotes colonization resistance against C. difficile through metabolism of bile acids to both reduce primary bile acids, which promote C. difficile spore germination, and increase secondary bile acids, which inhibit C. difficile vegetative growth.”
From Role of the gut microbiota in nutrient competition and protection against intestinal pathogen colonization (2023) · cites this paper as [54]

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Authors: Sorg, J. A., & Sonenshein, A. L.
Affiliations: Tufts University (US)
Corresponding author: Sonenshein, Abraham L.
ORCID: Sorg, Joseph A.
Sonenshein, Abraham L.
Venue: Journal of Bacteriology
Publisher: American Society for Microbiology
Published: 2010-10
Volume: 192
Issue: 19
Pages: 4983-4990
ISSN: 0021-9193 (ISSN-L)
1098-5530
DOI: 10.1128/jb.00610-10
PMC: PMC2944524
OpenAlex: W2097297514
Cited by: 332
References: 56
Citations by year: 2026: 18 · 2025: 24 · 2024: 17 · 2023: 22 · 2022: 26 · 2021: 23 · 2020: 29 · 2019: 22 · 2018: 35 · 2017: 20 · 2016: 34 · 2015: 18 · 2014: 19 · 2013: 12 · 2012: 7
FWCI: 5.18
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Journal of Bacteriology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (n01ai30050-20-0-3, N01-AI-30050)
National Institute of General Medical Sciences (K12GM074869)
National Institute of Allergy and Infectious Diseases (N01 AI030050)
Topics: Health Sciences › Medicine › Infectious Diseases › Clostridium difficile and Clostridium perfringens research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Bacterial Identification and Susceptibility Testing
Keywords: Clostridium difficile, spore germination, chenodeoxycholic acid, bile acids, taurocholate, competitive inhibition, Michaelis-Menten kinetics, 7α-dehydroxylation, Clostridium scindens, colonic microbiota, glycine
MeSH terms: Bile Acids and Salts, Chenodeoxycholic Acid, Chromatography, High Pressure Liquid, Spores, Bacterial, Taurocholic Acid, Clostridioides difficile

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Inhibiting the Initiation of Clostridium difficile Spore Germination using Analogs of Chenodeoxycholic Acid, a Bile Acid

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