Identification and Characterization of a Bile Acid 7α-Dehydroxylation Operon in Clostridium sp. Strain TO-931, a Highly Active 7α-Dehydroxylating Strain Isolated from Human Feces
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Clostridium sp. strain TO-931 can rapidly convert the primary bile acid cholic acid to a potentially toxic compound, deoxycholic acid. Mixed oligonucleotide probes were used to isolate a gene fragment encoding a putative bile acid transporter from Clostridium sp. strain TO-931. This DNA fragment had 60% nucleotide sequence identity to a known bile acid transporter gene from Eubacterium sp. strain VPI 12708, another bile acid-7α-dehydroxylating intestinal bacterium. The DNA (9.15 kb) surrounding the transporter gene was cloned from Clostridium sp. strain TO-931 and sequenced. Within this larger DNA fragment was a 7.9-kb region, containing six successive open reading frames (ORFs), that was encoded by a single 8.1-kb transcript, as determined by Northern blot analysis. The gene arrangement and DNA sequence of the Clostridium sp. strain TO-931 operon are similar to those of a Eubacterium sp. strain VPI 12708 bile acid-inducible operon containing nine ORFs. Several genes in the Eubacterium sp. strain VPI 12708 operon have been shown to encode products required for bile acid 7α-dehydroxylation. In Clostridium sp. strain TO-931, genes potentially encoding bile acid-coenzyme A (CoA) ligase, 3α-hydroxysteroid dehydrogenase, bile acid 7α-dehydratase, bile acid-CoA hydrolase, and a bile acid transporter were similar in size and exhibited amino acid homology to similar gene products from Eubacterium sp. strain VPI 12708 (encoded by baiB , baiA , baiE , baiF , and baiG , respectively). However, no genes similar to Eubacterium sp. strain VPI 12708 biaH or baiI were found in the Clostridium sp. strain TO-931 bai operon, and the two putative Eubacterium sp. strain VPI 12708 genes, baiC and baiD , were arranged in one continuous ORF in Clostridium sp. strain TO-931. Intergene regions showed no significant DNA sequence similarity, but primer extension analysis identified a region 115 bp upstream from the first ORF that exhibited 58% identity to a bai operator/promoter region identified in Eubacterium sp. strain VPI 12708. These results indicate that the gene organization, gene product amino acid sequences, and promoters of the bile acid-inducible operons of Clostridium sp. strain TO-931 and Eubacterium sp. strain VPI 12708 are highly conserved.
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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 [55]
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 [55]
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- Authors
- Wells, J. E., & Hylemon, P. B.
- Affiliations
- Virginia Commonwealth University (US)
- Venue
- Applied and Environmental Microbiology
- Publisher
- American Society for Microbiology
- Published
- 2000-03
- Volume
- 66
- Issue
- 3
- Pages
- 1107-1113
- ISSN
- 0099-2240 (ISSN-L)
- 1098-5336
- PMC
- PMC91949
- OpenAlex
- W2111642319
- Cited by
- 154
- References
- 36
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 9 · 2023: 11 · 2022: 8 · 2021: 13 · 2020: 7 · 2019: 9 · 2018: 19 · 2017: 5 · 2016: 8 · 2015: 7 · 2014: 7 · 2013: 7 · 2012: 2
- FWCI
- 0.60
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Applied and Environmental Microbiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (P01DK038030, P01 DK 38030, F32DK009750, F32DK-09750)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Steroid Chemistry and Biochemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- deoxycholic acid, cholic acid, bile acid transporters, 3α-hydroxysteroid dehydrogenase, gene structure, human fecal bacteria
- MeSH terms
- Amino Acid Sequence, Bacterial Proteins, Base Sequence, Bile Acids and Salts, Carrier Proteins, Cloning, Molecular, Clostridium, Coenzyme A Ligases, Feces, Genes, Bacterial, Humans, Hydro-Lyases, Hydroxysteroid Dehydrogenases, Intestines, Membrane Glycoproteins, Molecular Sequence Data, Operon, Promoter Regions, Genetic, Thiolester Hydrolases, 3-Hydroxysteroid Dehydrogenases, Gene Expression Regulation, Bacterial, Sequence Homology, Amino Acid, Sequence Analysis, DNA, Organic Anion Transporters, 3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)
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