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.
Highlights
The diarrheal disease cholera remains a major problem in developing countries
Because the cholera toxin is primarily responsible for the severe symptoms that are associated with the disease, our study highlights the negative effects of glucose-based oral rehydration therapy (ORT)
This study aimed to investigate how different carbon sources that are used for cholera treatment influence the production of the major virulence determinants in V. cholerae, cholera toxin (CT) and the toxin-coregulated pilus (TCP)(Fig. 1)
Summary
The diarrheal disease cholera remains a major problem in developing countries. In 2012, almost 250’000 cases were reported to the WHO; estimated numbers, including non-reported cases, are argued to reach several million cases every year. The recent disease outbreak in Haiti demonstrated the devastating effects of cholera epidemics Because of these dramatic consequences, the problem of how to stop an epidemic at an early stage, or at least to slow it down, was addressed and the employment of general intervention strategies was discussed. The general treatment of cholera patients is based on a so-called oral rehydration therapy (ORT), which is a cost-effective and applicable method to replace lost fluids and electrolytes. For the latter purpose, the administered solution contains a mixture of several compounds that were designated oral rehydration salts (ORS), including sodium, chloride, and potassium ions as well as glucose. A meta-analysis comparing the treatment with standard, glucose-based versus rice-based ORS illustrated the beneficial effects of the latter composition, such as reduced episodes of vomiting, a decrease of the stool volume, and a shortened recovery time [9,10,11,12]
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