Genomic signatures of coevolving phage-bacteria interaction networks

In diverse natural communities, cells and phages interact with many potential partners, but the impacts of pairwise coevolution on the overall structure of phage-bacteria interaction networks (PBINs) is not fully understood. Here, we conducted multiple pairwise coevolution experiments and examined how coevolution with one partner could simultaneously influence interactions with other partners. We then analyzed the underlying genetic changes that alter interactions in a large cross-experiment PBIN. The results reveal that interactions at the cell surface as well as intracellular interactions can alter patterns across the PBIN. When phages utilized the same set of host cell-surface receptor genes, pairwise coevolution with one partner did alter interactions with other partners. In contrast, if different sets of host cell-surface receptor genes were used, modular patterns in the cross-experiment PBIN were generally observed. On the phage side, resistance-breaking mutations arose in many putative receptor-binding proteins, and these changes could alter interactions with other hosts. However, in both the hosts and phages, over half of the mutated genes were not associated with cell-surface interactions. Host mutations likely altering intracellular phage-host interactions, including translation, protein stability, and DNA replication often led to broad resistance across the PBIN. In phages, mutations occurring in genes encoding endolysins, DNA methylases, oxygenases, transcriptional regulators, and tRNAs were observed potentially also influencing intracellular interactions. Based on these results, we propose a model to illustrate how these two different types of genetic signatures (i.e. extracellular cell-surface interactions verses intracellular interactions) can impact the structure of PBINs.