Abstract
Actinobacteriophages are viruses that infect bacterial hosts in the phylum Actinobacteria. More than 17,000 actinobacteriophages have been described and over 3,000 complete genome sequences reported, resulting from large-scale, high-impact, integrated research-education initiatives such as the Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Sciences (SEA-PHAGES) program. Their genomic diversity is enormous; actinobacteriophages comprise many architecturally mosaic genomes with distinct DNA sequences. Their genome diversity is driven by the highly dynamic interactions between phages and their hosts, and prophages can confer a variety of systems that defend against attack by genetically distinct phages; phages can neutralize these defense systems by coding for counter-defense proteins. These phages not only provide insights into diverse and dynamic phage populations but also have provided numerous tools for mycobacterial genetics. A case study using a three-phage cocktail to treat a patient with a drug-resistant Mycobacterium abscessus suggests that phages may have considerable potential for the therapeutic treatment of mycobacterial infections.