The application of a phage cocktail to prevent infectious disease: characterizing the impact of virulent bacteriophages on Vibrio cholerae infection.


Lynne Cairns1, Minmin Yen1, Andrew Camilli1, 2

1Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, United States
2Howard Hughes Medical Institute, United States


Cholera, caused by the facultative pathogen, Vibrio cholerae, is a major infectious disease in developing and disaster-stricken countries. There are an estimated 1-4 million cases resulting in 42,000-100,000 deaths per year. Household contacts of an individual suffering from cholera are 10-100 times more likely to contract the infection themselves. Household transmission could therefore present a critical point for clinical intervention by administration of prophylactic therapies. Virulent bacteriophages impact the dynamics of cholera infections. Three virulent phages, ICP1, ICP2 and ICP3, previously isolated from patient stool samples in Bangladesh, specifically target V. cholerae. We proposed that the combination of these three phages in a cocktail could be used as a prophylactic measure to prevent cholera. As a highly specific antimicrobial strategy, phage therapy has gained traction in recent years due to the current antibiotic crisis. By using a cocktail approach, we hope to limit the survival of genetically resistant V. cholerae cells. Using the infant mouse model of V. cholerae colonization, we have shown that the ICP cocktail is more effective in preventing colonization of the intestinal tract than any of the phages in isolation. Furthermore, the ICP cocktail effectively reduces colonization when administered up to 24 hours before infection with V. cholerae. Using the infant rabbit model of V. cholerae infection, we showed that the ICP phages significantly reduce the load of V. cholerae in the intestine when administered up to 24 hours prior to infection. Crucially, the phages are also effective in preventing the onset of cholera symptoms in these animals, namely; weight loss, accumulation of cecal fluid and the excretion of rice-water stool. Collectively, these experiments provide a proof-of-principle study into the usefulness of a phage cocktail in preventing an infectious bacterial disease.






Reference:
Poster Day 4-T12-Pos-44
Session:
Posters Covering the use of viruses to control infection and Processes governing the applied use of viruses
Presenters:
Lynne Cairns
Session:
Day 4 Posters Covering: The use of viruses to control infection and Processes governing the applied use of viruses
Presentation type:
Poster presentation
Room:
Poster Halls
Date:
Thursday, 21 July 2016
Time:
12:05 - 15:30