P. Li, J. Ni
Myxobacteria are social Gram-negative bacteria that perform cooperative predation and form multicellular fruiting bodies, serving as promising biocontrol agents against drug-resistant pathogens. Their associated viruses are therefore important ecological regulators, yet remain largely unexplored. Here, we applied CRISPR spacer-based host-virus linkage analysis to 3,229 myxobacterial genomes and identified 790 nonredundant myxophages spanning diverse global ecosystems. Comparative genomic analyses revealed extensive diversity in the taxonomy, lifestyles, and functional potential of these myxophages. We found that myxophages encode auxiliary metabolic genes involved in carbon, sulfur, iron, and cell-envelope metabolism, which may modulate host physiological processes during infection. Gene-sharing networks, whole-proteome phylogenies, inter-genomic and proteome comparison further identified six previously undescribed myxoviral lineages (MV-1~MV-6), each represented by complete genomes. Detailed analyses revealed the mechanisms by which these viruses hijack host cellular machinery and reprogram host processes. Notably, MV-1 encodes immune modulators, including the anti-CRISPR protein AcrIIA15 and a Cas12m effector located adjacent to CRISPR arrays, empower myxophages with sophisticated immune evasion and host interference strategies. This study substantially expands the myxoviral diversity and provides insights into virus-host interactions and evolutionary adaptation of myxophages.