Abstract

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 7-11G (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.

Highlights

  • Phenotypic heterogeneity is a fundamental survival strategy applied by many microorganisms for the rapid adaptation to changing environments and selective pressures

  • Our analysis identified a region with varying gene content consisting of two to five conserved open reading frames (ORFs) of unknown function located between a putative antiholin (Zampara et al, 2020) and a putative recombination endonuclease (Figure 1A)

  • RBP2 is required for infection of C. jejuni when the phase-variable MeOPN receptor is not expressed We previously demonstrated that phage F336 is completely dependent on the phase-variable MeOPN receptor for infection of C. jejuni (Sørensen et al, 2011)

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Summary

Introduction

Phenotypic heterogeneity is a fundamental survival strategy applied by many microorganisms for the rapid adaptation to changing environments and selective pressures. Phase variation creates a highly dynamic population and is essential for niche adaptation, in particular for host-associated bacteria, by promoting variable expression of surface structures (Jiang et al, 2019). Because those surface structures function as receptors for natural predators of bacteria,i.e., phages, phase variation can affect phage infection and is considered an important phage-resistance mechanism (Cota et al, 2015; Furi et al, 2019; Seed et al, 2012; Turkington et al, 2019; Zaleski et al, 2005). Phages are able to efficiently infect such bacterial hosts, and it is still not fully understood how phages have evolved to overcome the highly diverse and changing surface that results from phase-variable gene expression in bacteria

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