ArticleProceedings of the National Academy of Sciences of the United States of America2014
Bile salts act as effective protein-unfolding agents and instigators of disulfide stress in vivo.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 150 citations in OpenAlex.
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- Cold-Pressing Sunflower Meal and Gastric pH Synergistically ImproveJournal of agricultural and food chemistry · 2026Article
- Impact of Lipophilicity-Tuning on the Antimicrobial Activity of a Series of β-Face-Expanding Bile Acid Derivatives.BioMed research international · 2026Article
- Boosting buccal drug absorption: Mechanistic insights into bilosome-mediated delivery.International journal of pharmaceutics: X · 2025Article
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- MalS, a periplasmic α-amylase in Escherichia coli, has a binding affinity to glycogen with unique substrate specificities.Applied microbiology and biotechnology · 2025Article
- TUDCA modulates drug bioavailability to regulate resistance to acute ER stress inMolecular biology of the cell · 2025Article
- Recent Advances in the Understanding of Stress Resistance Mechanisms in Probiotics: Relevance for the Design of Functional Food Systems.Probiotics and antimicrobial proteins · 2025Review
- The Effect of glycocholic acid on the growth, membrane permeability, conjugation and antibiotic susceptibility of Enterobacteriaceae.Frontiers in cellular and infection microbiology · 2025Article
- Bile acids and gut microbiota: interactions and impacts on polycystic ovary syndrome.Frontiers in microbiomes · 2025Review
- Genomic personalities ofISME communications · 2025Article
- AcrAB Efflux Pump Plays a Crucial Role in Bile Salts Resistance and Pathogenesis ofAntibiotics (Basel, Switzerland) · 2024Article
- Periplasmic Chaperones: Outer Membrane Biogenesis and Envelope Stress.Annual review of microbiology · 2024Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Commensal and pathogenic bacteria must deal with many different stress conditions to survive in and colonize the human gastrointestinal tract. One major challenge that bacteria encounter in the gut is the high concentration of bile salts, which not only aid in food absorption but also act as effective physiological antimicrobials. The mechanism by which bile salts limit bacterial growth is still largely unknown. Here, we show that bile salts cause widespread protein unfolding and aggregation, affecting many essential proteins. Simultaneously, the bacterial cytosol becomes highly oxidizing, indicative of disulfide stress. Strains defective in reducing oxidative thiol modifications, restoring redox homeostasis, or preventing irreversible protein aggregation under disulfide stress conditions are sensitive to bile salt treatment. Surprisingly, cholate and deoxycholate, two of the most abundant and very closely related physiological bile salts, vary substantially in their destabilizing effects on proteins in vitro and cause protein unfolding of different subsets of proteins in vivo. Our results provide a potential mechanistic explanation for the antimicrobial effects of bile salts, help explain the beneficial effects of bile salt mixtures, and suggest that we have identified a physiological source of protein-unfolding disulfide stress conditions in bacteria.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.