Abstract Although it is generally accepted that viruses (phages) drive bacterial evolution, how these dynamics play out in the wild remains poorly understood. Here we show that the arms race between phages and their hosts 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 afforded by multiple elements is cumulative, and a single bacterial genome can harbor as many as 18 putative phage-defense elements. Overall, elements account for 90% of the flexible genome amongst closely related strains. The rapid turnover of these elements demonstrates that phage resistance is unlinked from other genomic features and that resistance to phage therapy might be as easily acquired as antibiotic resistance.

Rapid evolutionary turnover of mobile genetic elements drives microbial resistance to viruses