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bioRxiv · 10.1101/2025.04.01.646652

Filamentous cheater phages drive bacterial and phage populations to lower fitness

Kubota, N. S.·Scribner, M. R.·Cooper, V. S.
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Abstract

Many bacteria carry phage genome(s) in their chromosome, which intertwines the fitness of the bacterium and the phage. Most Pseudomonas aeruginosa strains carry filamentous phages called Pf that establish chronic infections and do not require host lysis to spread. However, spontaneous mutations in the Pf repressor gene (pf5r) can allow extreme phage production that slows bacterial growth and increases cell death, violating an apparent detente between bacterium and phage. We observed this paradoxical outcome in an evolution experiment with P. aeruginosa in media simulating nutrients from the cystic fibrosis airway. Bacteria containing pf5r mutant phage grow to a lower density but directly outcompete their ancestor and convert them into pf5r mutants via phage superinfection. Reduced fitness therefore spreads throughout the bacterial population, driven by weaponized Pf. Yet high intracellular phage replication facilitates another evolutionary conflict: "cheater miniphages" lacking capsid genes and the superinfection exclusion gene (pfsE) invade populations of full-length phages within cells. Although bacteria containing both full-length phages and miniphages are most immune to superinfection by limiting the Pf receptor, this hybrid vigor is extremely unstable, as a classic Tragedy of the Commons scenario ensues that causes complete prophage loss. The entire cycle - from phage hyperactivation to miniphage invasion to prophage loss - can occur within 24h, showcasing rapid coevolution between bacteria and their filamentous phages. This study demonstrates that P. aeruginosa, and potentially many other bacterial species that carry filamentous prophages, risk being exploited by these phages in a runaway process that reduces fitness of both host and virus. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=168 SRC="FIGDIR/small/646652v4_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@1f3d9c9org.highwire.dtl.DTLVardef@5f5591org.highwire.dtl.DTLVardef@eac39borg.highwire.dtl.DTLVardef@d00f3a_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Kubota, N. S., Scribner, M. R., Cooper, V. S.. 2025-04-01. Filamentous cheater phages drive bacterial and phage populations to lower fitness. https://doi.org/10.1101/2025.04.01.646652

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