The enemy from within: a prophage ofRoseburia intestinalissystematically turns lytic in the mouse gut, driving bacterial adaptation by CRISPR spacer acquisition

Abstract

AbstractDespite an overall stability in time of the human gut microbiota at the phylum level, strong temporal variations in species abundance have been observed. We are far from a clear understanding of what promotes or disrupts the stability of microbiome communities. Environmental factors, like food or antibiotic use, modify the gut microbiota composition, but their overall impacts remain relatively low. Phages, the viruses that infect bacteria, might constitute important factors explaining temporal variations in species abundance. Gut bacteria harbour numerous prophages, or dormant viruses. A breakdown of prophage dormancy can evolve through the selection of ultravirulent phage mutants, potentially leading to important bacterial death. Whether such phenomenon occurs in the mammal’s microbiota has been largely unexplored.Here we studied temperate phage-bacteria coevolution in gnotoxenic mice colonised withEscherichia coliandRoseburia intestinalis, a dominant symbiont of the human gut microbiota. We show thatR. intestinalisharbors two active prophages, Jekyll and Shimadzu, and observed the systematic evolution of ultravirulent Shimadzu phage mutants, leading to a collapse ofR. intestinalispopulation. In a second step, phage infection drove the fast evolution of host phage-resistance mainly through phage-derived spacer acquisition in a Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) array. Alternatively, phage resistance was conferred by a prophage originating from an ultravirulent phage with a restored ability to lysogenize.Our results demonstrate that prophages are the potential source of ultravirulent phages that can successfully infect most of the susceptible bacteria. This suggests that prophages can play important roles in the short-term temporal variations observed in the composition of the gut microbiota.