Oral administration of bacteria-killing viruses prevents cholera infection in animal models.

Oral administration of viruses that specifically target cholera bacteria prevents infection and cholera-like symptoms in animal model experiments.Oral administration of a cocktail of three viruses, all of which specifically kill cholera bacteria, prevents infection and cholera-like symptoms in animal model experiments, report scientists from Tufts University School of Medicine (TUSM) and the Sackler School of Graduate Biomedical Sciences at Tufts in Nature Communications The findings are the first to demonstrate the potential efficacy of bacteria-killing viruses—known as bacteriophages, or phages—as an orally administered preventive therapy against an acute gastrointestinal bacterial disease. Camilli and colleagues searched for phages that are specific for Vibrio cholerae, the bacterium that causes cholera—a potentially lethal infectious disease marked by severe diarrhea and dehydration. While phages that kill V. cholerae are abundant in nature, the team identified three strains that uniquely retained the ability to kill V. cholerae within the small intestine, the site of infection in humans. These phages function by targeting bacterial surface receptors normally involved in infectiousness, making them ideal therapeutic candidates—to develop resistance, cholera bacteria must acquire mutations in these receptors, which cause the bacteria to become less infectious. The team carried out a series of experiments in small animal models of cholera to test the efficacy of these phages as a preventative treatment. Animals were given an oral dose of a cocktail containing all three phages, at time points ranging from three to 24 hours before infection with a standardized amount of V. cholerae bacteria. A preventative dose of the phage cocktail eliminated V. cholerae in the small intestines of over half of treated animals when given three hours before infection. In remaining animals, and for those treated up to 24 hours before infection, bacteria numbers were reduced 500-fold or more on average, compared to untreated controls. Overall, treatment was most effective in reducing bacterial load when given between three and 12 hours before infection. The team found no evidence of cholera-like diarrhea and no significant weight loss in treated animals.