Temperate phages are common, and prophages are abundant residents of sequenced bacterial genomes. Mycobacteriophages are viruses that infect mycobacterial hosts including Mycobacterium tuberculosis and Mycobacterium smegmatis, encompass substantial genetic diversity and are commonly temperate. Characterization of ten Cluster N temperate mycobacteriophages revealed at least five distinct prophage-expressed viral defence systems that interfere with the infection of lytic and temperate phages that are either closely related (homotypic defence) or unrelated (heterotypic defence) to the prophage. Target specificity is unpredictable, ranging from a single target phage to one-third of those tested. The defence systems include a single-subunit restriction system, a heterotypic exclusion system and a predicted (p)ppGpp synthetase, which blocks lytic phage growth, promotes bacterial survival and enables efficient lysogeny. The predicted (p)ppGpp synthetase coded by the Phrann prophage defends against phage Tweety infection, but Tweety codes for a tetrapeptide repeat protein, gp54, which acts as a highly effective counter-defence system. Prophage-mediated viral defence offers an efficient mechanism for bacterial success in host–virus dynamics, and counter-defence promotes phage co-evolution.
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The authors thank the many students in the SEA-PHAGES programme that contributed to the isolation, annotation and characterization of the phages described here. Specific contributions are noted at http://phagesdb.org. The authors thank J. Schiebel, A. Jonas, T. Stoner, D. Green, R. Rush and L. Lin for help with escape mutant isolation, C.-C. Ko for help with plasmid construction and D. Asai, V. Sivanathan, K. Bradley and L. Barker for support of the SEA-PHAGES programme. This work was supported by grants from the National Institutes of Health (GM116884) and the Howard Hughes Medical Institute (54308198) to G.F.H. and a National Science Foundation pre-doctoral fellowship to T.N.M. (no. 1247842).
The authors declare no competing financial interests.
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Dedrick, R., Jacobs-Sera, D., Bustamante, C. et al. Prophage-mediated defence against viral attack and viral counter-defence. Nat Microbiol 2, 16251 (2017). https://doi.org/10.1038/nmicrobiol.2016.251
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