Disinfectant Stress Enhances Prokaryotic Symbiosis with Lysogenic Phages and Defense Systems Against Detrimental Phage Infection

Abstract Background Mutualistic symbiosis is critical for microbial adaptation to stress and microbiome functions. Recent progress in metagenomics has advanced understanding of prokaryote-phage symbiosis and the ecological and evolutionary significance of viromes. However, it remains elusive how prokaryotic antiviral systems respond to symbiosis with lysogenic phages and its implications to microbial ecosystem services. Microbiomes in drinking water distribution systems (DWDS) under disinfectant stress are an important platform to study the ecological drivers and effects of prokaryote-phage symbiosis. Results Enhanced prokaryote-phage mutualism was observed in the microbiome of 7 DWDS under disinfectant stress relative to 5 control DWDS without disinfection. The relative abundance of lysogenic phages increased in microbiomes in DWDS with residual chlorine. Prokaryote-phage linkage analysis revealed that residual chlorine enriched phages that reproduced in disinfectant-tolerant prokaryotes, and selected for broad-host-range phages that could propagate using multiple hosts. Moreover, the virome under disinfectant stress harbored high levels of auxiliary metabolic genes (AMGs) encoding reductase, which could alleviate oxidative stress. Various prokaryotic antiviral systems were elevated under disinfectant stress, particularly the Restriction-Modification (RM) and CRISPR-Cas systems. Some enriched RM and CRISPR-Cas systems were linked to lysogenic phages and prophages, inferring that these antiviral systems are compatible with phage infections with mutualistic potential. In addition, RM systems harbored in lysogenic phages and prophages were enriched in the disinfected DWDS virome. This apparently benefited lysogenic phages to evade prokaryotic antiviral systems through RM-mediated methylation of phage DNA. Transduction of antiviral genes would also empower the hosts with additional capability to defend against secondary infections by lytic phages. Conclusion This metagenomic study infers that sublethal residual disinfectants can enhance prokaryote-phage mutualism, and enrich some prokaryotic antiviral systems to defend against detrimental (lytic) phage infection. Our study advances understanding of the development, maintenance and overlooked implications of prokaryote-phage mutualism, which offers new perspectives for microbiome adaptation under environmental stress.