A cocktail of three virulent bacteriophages prevents Vibrio cholerae infection in animal models.
Effective prevention strategies will be essential in reducing disease burden due to bacterial infections. Here we harness the specificity and rapid-acting properties of bacteriophages as a potential prophylaxis therapy for cholera, a severely dehydrating disease caused by Vibrio cholerae. To this end, we test a cocktail of three virulent phages in two animal models of cholera pathogenesis (infant mouse and rabbit models). Oral administration of the phages up to 24 h before V. cholerae challenge reduces colonization of the intestinal tract and prevents cholera-like diarrhea. None of the surviving V. cholerae colonies are resistant to all three phages. Genome sequencing and variant analysis of the surviving colonies indicate that resistance to the phages is largely conferred by mutations in genes required for the production of the phage receptors. For acute infections, such as cholera, phage prophylaxis could provide a strategy to limit the impact of bacterial disease on human health.
Department of Molecular Biology and Microbiology, Howard Hughes Medical Institute, Tufts University School of Medicine, 136 Harrison Avenue, Boston, Massachussetts 02111, USA.|Program in Molecular Microbiology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, Massachussetts 02111, USA.
Minmin
M
Yen
Department of Molecular Biology and Microbiology, Howard Hughes Medical Institute, Tufts University School of Medicine, 136 Harrison Avenue, Boston, Massachussetts 02111, USA.
Lynne S
0000-0002-0970-9943
LS
Cairns
Department of Molecular Biology and Microbiology, Howard Hughes Medical Institute, Tufts University School of Medicine, 136 Harrison Avenue, Boston, Massachussetts 02111, USA.
Andrew
A
Camilli
D000818:Animals; D058491:Bacterial Load; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001435:Bacteriophages / Q000472:pathogenicity*; D002771:Cholera / Q000382:microbiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D041981:Gastrointestinal Tract / Q000382:microbiology; D006801:Humans; D051379:Mice; D023421:Models, Animal; D009154:Mutation; D011817:Rabbits; D014734:Vibrio cholerae / Q000235:genetics / Q000502:physiology / Q000821:virology*; D014774:Virulence
D001426:Bacterial Proteins