Abstract

Description Wild phage evolution Bacteria possess a diversity of highly specific phage defense mechanisms that evolve rapidly and that account for a large proportion of bacterial genomes. These dynamics must be understood if phage therapy is to be seriously considered for clinical use. Hussain et al. studied a set of nearly clonal wild-caught Vibrio lentus hosts and their phage and found that the hosts segregated into two groups infected by different viruses (see the Perspective by Meaden and Fineran). Puzzlingly, both host groups have the same surface phage receptors. This apparent paradox was resolved by sequencing of the hosts, which revealed distinct suites of endogenous but mobile phage defense elements (PDEs) in the two host phenotypes. Indeed, the PDEs constitute a large fraction of the flexible noncore genome of the bacteria. This means the PDEs can evolve and transfer from cell to cell without interfering with metabolic processes required to synthesize essential cell surface molecules. —CA For wild microbes, horizontal gene transfer of phage-defense elements decouples phage resistance from host core function. Although it is generally accepted that phages drive bacterial evolution, how these dynamics play out in the wild remains poorly understood. We found that susceptibility to viral killing in marine Vibrio is mediated by large and highly diverse mobile genetic elements. These phage defense elements display exceedingly fast evolutionary turnover, resulting in differential phage susceptibility among clonal bacterial strains while phage receptors remain invariant. Protection is cumulative, and a single bacterial genome can harbor 6 to 12 defense elements, accounting for more than 90% of the flexible genome among close relatives. The rapid turnover of these elements decouples phage resistance from other genomic features. Thus, resistance to phages in the wild follows evolutionary trajectories alternative to those predicted from laboratory-based evolutionary experiments.