Longitudinal multi-omics reveal phase-dependent viral adaptive strategies and functional potential during formation...

Virus-prokaryote interactions within microbial aggregates critically influence microbiome function and stability, yet the interactive dynamics during microbial aggregation remain largely unexplored. Here, longitudinal multi-omics revealed that prokaryotic host community diversity underwent decline and subsequent recovery during algal-bacterial granular sludge (ABGS) formation from activated sludge. Declined host diversity in the collapse phase enriched for lysogenic viruses and facilitated virus-host mutualistic symbiosis, during which the proportion of lysogenic metagenome-assembled genomes (MAGs) peaked at 84% (841,649 TPM), with auxiliary metabolic genes (AMGs) primarily involved in genetic information processing and amino acid metabolism. Moreover, low host diversity increased viral microdiversity by 1.97-fold and selected for virion structure genes that were conducive to viral fitness and replication. As host diversity recovered during the recovery phase, viruses and hosts engaged in an evolutionary arms race, with both host defense systems (DS) (Spearman's Rho = 0.68, P < 0.05) and viral anti-defense systems (ADS) (Spearman's Rho = 0.51, P < 0.05) enriched along with granule maturation. Furthermore, active lysogenic infections were accompanied by the dissemination of AMGs predominantly associated with the metabolism of cofactors, vitamins, terpenoids, and polyketides. Despite their phase-dependent functional profiles, lysogenic phages with AMGs putatively enhanced the structural and functional stability of the microbiome during ABGS formation. Overall, our study unveils a phase-dependent co-evolutionary interplay between viruses and prokaryotic hosts during ABGS formation, providing insights into virus-mediated microbial structural and functional resilience in engineered ecosystems.