ArticleInfection and immunity2009
Bicarbonate Induces Vibrio cholerae virulence gene expression by enhancing ToxT activity.
Article in Infection and immunity, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 113 papers.
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Who cites it
113 citing papers in PubMed, 185 citations in OpenAlex.
- Environmental regulation of virulence in Vibrio cholerae: integrating multi-omics, predictive models, and comparative insights across emerging Vibrio species.Gut pathogens · 2026Review
- Type IV pilin regulation: a transcriptional overview.Critical reviews in microbiology · 2026Review
- Roles of three carbonic anhydrases inFEMS microbes · 2026Article
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- Development of Penicillin-Based Carbonic Anhydrase Inhibitors Targeting Multidrug-ResistantJournal of medicinal chemistry · 2024Article
- Benzothiadiazinone-1,1-Dioxide Carbonic Anhydrase Inhibitors Suppress the Growth of Drug-ResistantInternational journal of molecular sciences · 2024Article
- Benzenesulfonamide derivatives asJournal of enzyme inhibition and medicinal chemistry · 2023Article
- Expression of Cholera Toxin (CT) and the Toxin Co-Regulated Pilus (TCP) by Variants of ToxT inToxins · 2023Article
- Collateral Changes in Cell Physiology Associated with ADC-7 β-Lactamase Expression in Acinetobacter baumannii.Microbiology spectrum · 2023Article
- Carbonic Anhydrase Inhibitors as Novel Antibacterials in the Era of Antibiotic Resistance: Where Are We Now?Antibiotics (Basel, Switzerland) · 2023Review
- Review
- Carbonic anhydrase versatility: from pH regulation to COFrontiers in molecular biosciences · 2023Article
- Advances in cholera research: from molecular biology to public health initiatives.Frontiers in microbiology · 2023Review
- Dithiocarbamates effectively inhibit the α-carbonic anhydrase fromJournal of enzyme inhibition and medicinal chemistry · 2022Article
- The gram-negative bacteriumJournal of enzyme inhibition and medicinal chemistry · 2022Article
- A mannose-sensing AraC-type transcriptional activator regulates cell-cell aggregation of Vibrio cholerae.NPJ biofilms and microbiomes · 2022Article
53 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Vibrio cholerae is a gram-negative bacterium that is the causative agent of cholera, a severe diarrheal illness. The two biotypes of V. cholerae O1 capable of causing cholera, classical and El Tor, require different in vitro growth conditions for induction of virulence gene expression. Growth under the inducing conditions or infection of a host initiates a complex regulatory cascade that results in production of ToxT, a regulatory protein that directly activates transcription of the genes encoding cholera toxin (CT), toxin-coregulated pilus (TCP), and other virulence genes. Previous studies have shown that sodium bicarbonate induces CT expression in the V. cholerae El Tor biotype. However, the mechanism for bicarbonate-mediated CT induction has not been defined. In this study, we demonstrate that bicarbonate stimulates virulence gene expression by enhancing ToxT activity. Both the classical and El Tor biotypes produce inactive ToxT protein when they are cultured statically in the absence of bicarbonate. Addition of bicarbonate to the culture medium does not affect ToxT production but causes a significant increase in CT and TCP expression in both biotypes. Ethoxyzolamide, a potent carbonic anhydrase inhibitor, inhibits bicarbonate-mediated virulence induction, suggesting that conversion of CO(2) into bicarbonate by carbonic anhydrase plays a role in virulence induction. Thus, bicarbonate is the first positive effector for ToxT activity to be identified. Given that bicarbonate is present at high concentration in the upper small intestine where V. cholerae colonizes, bicarbonate is likely an important chemical stimulus that V. cholerae senses and that induces virulence during the natural course of infection.
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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.