title: Glucose- but not rice-based oral rehydration therapy enhances the production of virulence determinants in the human pathogen Vibrio cholerae.
abstract: Despite major attempts to prevent cholera transmission, millions of people worldwide still must address this devastating disease. Cholera research has so far mainly focused on the causative agent, the bacterium Vibrio cholerae, or on disease treatment, but rarely were results from both fields interconnected. Indeed, the treatment of this severe diarrheal disease is mostly accomplished by oral rehydration therapy (ORT), whereby water and electrolytes are replenished. Commonly distributed oral rehydration salts also contain glucose. Here, we analyzed the effects of glucose and alternative carbon sources on the production of virulence determinants in the causative agent of cholera, the bacterium Vibrio cholerae during in vitro experimentation. We demonstrate that virulence gene expression and the production of cholera toxin are enhanced in the presence of glucose or similarly transported sugars in a ToxR-, TcpP- and ToxT-dependent manner. The virulence genes were significantly less expressed if alternative non-PTS carbon sources, including rice-based starch, were utilized. Notably, even though glucose-based ORT is commonly used, field studies indicated that rice-based ORT performs better. We therefore used a spatially explicit epidemiological model to demonstrate that the better performing rice-based ORT could have a significant impact on epidemic progression based on the recent outbreak of cholera in Haiti. Our results strongly support a change of carbon source for the treatment of cholera, especially in epidemic settings.
authors.affiliation: Laboratory of Molecular Microbiology, Global Health Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
authors.forename: Juliane
authors.initials: J
authors.lastname: Kühn
authors.affiliation: Laboratory of Ecohydrology, Environmental Engineering Institute, School of Architecture, Civil and Environmental Engineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
authors.forename: Flavio
authors.initials: F
authors.lastname: Finger
authors.affiliation: Laboratory of Ecohydrology, Environmental Engineering Institute, School of Architecture, Civil and Environmental Engineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertuzzo
authors.affiliation: Laboratory of Molecular Microbiology, Global Health Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Borgeaud
authors.affiliation: Dipartimento di Elettronica Informazione & Bioingegneria, Politecnico di Milano, Milan, Italy.
authors.forename: Marino
authors.initials: M
authors.lastname: Gatto
authors.affiliation: Laboratory of Ecohydrology, Environmental Engineering Institute, School of Architecture, Civil and Environmental Engineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland; Dipartimento ICEA, Universitá di Padova, Padova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Rinaldo
authors.affiliation: Laboratory of Molecular Microbiology, Global Health Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
authors.forename: Melanie
authors.initials: M
authors.lastname: Blokesch
mesh_terms: D002771:Cholera / Q000453:epidemiology / Q000628:therapy*; D005440:Fluid Therapy; D005947:Glucose / Q000378:metabolism*; D006205:Haiti / Q000453:epidemiology; D006801:Humans; D008962:Models, Theoretical; D012275:Oryza; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System / Q000378:metabolism; D053038:Quorum Sensing; D013213:Starch / Q000378:metabolism; D014734:Vibrio cholerae / Q000472:pathogenicity*; D037521:Virulence Factors / Q000235:genetics*
chemical_list: D037521:Virulence Factors; D013213:Starch; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System; D005947:Glucose