Characterization of a Novel Bile-Inducible Operon Encoding a Two-Component Regulatory System in Lactobacillus acidophilus
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Lactobacillus acidophilus NCFM is an industrially important strain used extensively as a probiotic culture. Tolerance of the presence of bile is an attribute important to microbial survival in the intestinal tract. A whole-genome microarray was employed to examine the effects of bile on the global transcriptional profile of this strain, with the intention of elucidating genes contributing to bile tolerance. Genes involved in carbohydrate metabolism were generally induced, while genes involved in other aspects of cellular growth were mostly repressed. A 7-kb eight-gene operon encoding a two-component regulatory system (2CRS), a transporter, an oxidoreductase, and four hypothetical proteins was significantly upregulated in the presence of bile. Deletion mutations were constructed in six genes of the operon. Transcriptional analysis of the 2CRS mutants showed that mutation of the histidine protein kinase (HPK) had no effect on the induction of the operon, whereas the mutated response regulator (RR) showed enhanced induction when the cells were exposed to bile. These results indicate that the 2CRS plays a role in bile tolerance and that the operon it resides in is negatively controlled by the RR. Mutations in the transporter, the HPK, the RR, and a hypothetical protein each resulted in loss of tolerance of bile. Mutations in genes encoding another hypothetical protein and a putative oxidoreductase resulted in significant increases in bile tolerance. This functional analysis showed that the operon encoded proteins involved in both bile tolerance and bile sensitivity.
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Exposure to bile does not necessarily induce bsh gene expression in BSH-active lactobacilli strains.
“This result is also consistent with previous works indicating that exposure to bile does not necessarily induce bsh gene expression in BSH-active lactobacilli strains [73, 86].”
From Bile Salt Hydrolase Activity in the Food-Derived Strain Levilactobacillus brevis M3R3: Genomic and Functional Characterization (2026) · cites this paper as [86]
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“This result is also consistent with previous works indicating that exposure to bile does not necessarily induce bsh gene expression in BSH-active lactobacilli strains [73, 86].”
- Authors
- Pfeiler, E. A., Azcarate-Peril, M. A., & Klaenhammer, T. R.
- Affiliations
- North Carolina State University (US)
- Department of Food Science, North Carolina State University, Raleigh, North Carolina 27695
- Venue
- Journal of Bacteriology
- Publisher
- American Society for Microbiology
- Published
- 2007-07
- Volume
- 189
- Issue
- 13
- Pages
- 4624-4634
- ISSN
- 0021-9193 (ISSN-L)
- 1098-5530
- PMC
- PMC1913432
- OpenAlex
- W2130243630
- Cited by
- 154
- References
- 39
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 10 · 2023: 3 · 2022: 9 · 2021: 8 · 2020: 11 · 2019: 7 · 2018: 6 · 2017: 9 · 2016: 6 · 2015: 4 · 2014: 6 · 2013: 6 · 2012: 6
- FWCI
- 5.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Bacteriology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Dairy Management
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Life Sciences › Immunology and Microbiology › Microbiology › Reproductive tract infections research
- Keywords
- Lactobacillus acidophilus NCFM, bile tolerance, two-component systems, response regulator, histidine kinase, transcriptional regulation, bile transporters, oxidative enzymes, probiotic bacteria, deletion mutants
- MeSH terms
- Bacterial Proteins, Base Sequence, Bile Acids and Salts, Genes, Bacterial, Lactobacillus acidophilus, Models, Genetic, Molecular Sequence Data, Mutation, Transcription, Genetic, Gene Expression Regulation, Bacterial, Mutagenesis, Site-Directed, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Gene Order
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