The value of a prophage-borne defense system in phage–phage competition
- 1Department of Physics, Ben-Gurion University of the Negev, Beer Sheva, Israel
- 2Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America
Abstract
Temperate phages that incorporate into their bacterial hosts’ genomes often encode defense systems that protect their hosts from superinfection by unrelated phages. Yet the evolutionary value of such defenses to the phage remains unclear. We present a minimal theoretical framework to quantify the selective advantage of a prophage-borne defense system in competition between temperate phages infecting the same bacterial host. The model reveals regimes in which a “defensive phage” can invade and persist despite growth costs, regimes of bistability, and others in which all phage types coexist due to a rock–paper–scissors-like dynamic between defensive, non-defensive, and defense-loss variants. Because defense systems can be non-transitive, true rock-paper-scissors relations can lead to persistent oscillations. These results identify simple conditions under which phage-encoded defense systems are evolutionarily stable, providing testable predictions for the prevalence and maintenance of these systems in natural microbial communities. Author summary: Bacteria are susceptible to their own viruses, called bacteriophages or simply phages. Temperate phages are able to integrate their DNA into bacterial genomes and persist as “prophages.” Surprisingly, many prophages encode defense systems that protect their bacterial host from infection by other phages. While such defenses are widespread in microbial genomes, it is not obvious why they benefit the prophage itself – especially because defense systems typically slow host growth or carry other costs. We developed a simple mathematical model to ask when a prophage-borne defense system is favored during competition between temperate phages infecting the same bacterial species. By focusing on long-term population dynamics, we identify conditions under which a “defensive” prophage can invade and persist, even if it reduces host growth by as much as 20%. If defense systems can be lost by mutation, a striking outcome emerges: defensive and non-defensive variants can stably coexist through a rock–paper–scissors-like interaction. Our results provide a quantitative framework for understanding why phage-encoded defense systems are so common in nature – they show that even costly defenses can be evolutionarily stable when phages frequently compete for the same hosts.
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BibTeX
@article{meir2026value,
title = {{The value of a prophage-borne defense system in phage–phage competition}},
author = {Yigal Meir and Ned S. Wingreen},
journal = {PLOS Computational Biology},
year = {2026},
month = sep,
doi = {10.1371/journal.pcbi.1014739},
url = {https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014739},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The value of a prophage-borne defense system in phage–phage competition
AU - Yigal Meir
AU - Ned S. Wingreen
PY - 2026
DA - 2026/09/08
JO - PLOS Computational Biology
DO - 10.1371/journal.pcbi.1014739
UR - https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014739
AB - Temperate phages that incorporate into their bacterial hosts’ genomes often encode defense systems that protect their hosts from superinfection by unrelated phages. Yet the evolutionary value of such defenses to the phage remains unclear. We present a minimal theoretical framework to quantify the selective advantage of a prophage-borne defense system in competition between temperate phages infecting the same bacterial host. The model reveals regimes in which a “defensive phage” can invade and persist despite growth costs, regimes of bistability, and others in which all phage types coexist due to a rock–paper–scissors-like dynamic between defensive, non-defensive, and defense-loss variants. Because defense systems can be non-transitive, true rock-paper-scissors relations can lead to persistent oscillations. These results identify simple conditions under which phage-encoded defense systems are evolutionarily stable, providing testable predictions for the prevalence and maintenance of these systems in natural microbial communities. Author summary: Bacteria are susceptible to their own viruses, called bacteriophages or simply phages. Temperate phages are able to integrate their DNA into bacterial genomes and persist as “prophages.” Surprisingly, many prophages encode defense systems that protect their bacterial host from infection by other phages. While such defenses are widespread in microbial genomes, it is not obvious why they benefit the prophage itself – especially because defense systems typically slow host growth or carry other costs. We developed a simple mathematical model to ask when a prophage-borne defense system is favored during competition between temperate phages infecting the same bacterial species. By focusing on long-term population dynamics, we identify conditions under which a “defensive” prophage can invade and persist, even if it reduces host growth by as much as 20%. If defense systems can be lost by mutation, a striking outcome emerges: defensive and non-defensive variants can stably coexist through a rock–paper–scissors-like interaction. Our results provide a quantitative framework for understanding why phage-encoded defense systems are so common in nature – they show that even costly defenses can be evolutionarily stable when phages frequently compete for the same hosts.
SN - 1553-7358
ER -