Adaptation to bile and anaerobicity limits Vibrio cholerae phage adsorption

Vibrio cholerae is the bacterial pathogen responsible for cholera, a diarrheal disease that impacts people in areas without access to potable water. In regions that lack such infrastructure, cholera represents a large proportion of disease outbreaks. Bacteriophages (phages, viruses that infect bacteria) have recently been examined as potential therapeutic and prophylactic agents to treat and prevent bacterial disease outbreaks like cholera due to their specificity and stability. This work examines the interaction between V. cholerae and vibriophages in consideration for a cholera prophylaxis regimen (M. Yen, L. S. Cairns, and A. Camilli, Nat Commun 8:14187, 2017, https://doi.org/10.1038/ncomms14187) in the context of stimuli found in the intestinal environment. We discover that common signals in the intestinal environment induce cell surface modifications in V. cholerae that also restrict some phages from binding and initiating infection. These findings could impact considerations for the design of phage-based treatments, as phage infection appears to be limited by bacterial adaptations to the intestinal environment.