Campylobacter phages use hypermutable polyG tracts to create phenotypic diversity and evade bacterial resistance

Phase variation is a common mechanism for creating phenotypic heterogeneity of surface structures in bacteria important for niche adaptation. In Campylobacter, phase variation occurs by random variation in hypermutable homonucleotide 7–11 G (polyG) tracts. To elucidate how phages adapt to phase-variable hosts, we study Fletchervirus phages infecting Campylobacter dependent on a phase-variable receptor. Our data demonstrate that Fletcherviruses mimic their host and encode hypermutable polyG tracts, leading to phase-variable expression of two of four receptor-binding proteins. This creates phenotypically diverse phage populations, including a sub-population that infects the bacterial host when the phase-variable receptor is not expressed. Such population dynamics of both phage and host promote co-existence in a shared niche. Strikingly, we identify polyG tracts in more than 100 phage genera, infecting more than 70 bacterial species. Future experimental work may confirm phase variation as a widespread strategy for creating phenotypically diverse phage populations. [Display omitted] •Fletchervirus phages encode four different receptor-binding proteins (RBP1–RBP4)•PolyG tracts promote phase-variable expression of RBP2 and RBP3•RBP2 allows phage infection when the MeOPN receptor is not expressed•PolyG tracts are found in more than 100 different phage genera Sørensen et al. show that Fletchervirus phages mimic their bacterial host and encode hypermutable polyG tracts that create phenotypically diverse phage populations that can overcome phage resistance. The presence of polyG tracts in more than 100 phage genera suggests that phenotypic diversity could be widespread but overlooked in phages.