MS07 - ECOP-03

Eco-evolutionary Dynamics of Bacteriophage

Thursday, July 17 at 3:50pm

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Joshua S. Weitz (University of Maryland, Department of Biology & Physics and U of Maryland Institute for Health Computing), Asher Leeks, University of British Columbia, Department of Zoology

Description:

Bacteriophage (‘phage’) are viruses that exclusively infect bacteria. Ecologically, phage infections release carbon and other nutrients back into the environment through lysing bacterial cells, thus driving biogeochemical cycles in the ‘microbial loop’. Evolutionarily, phages coevolve with their host bacteria and with other phages in complex ways, and can even establish persistent infections that benefit the bacterial host. Both ecological and evolutionary phage dynamics can shape microbiome composition, with far-reaching consequences for human health. Increasing evidence of phage impacts on environmental and health outcomes has spurred a renewal of theory and mathematical models to explore the eco-evolutionary dynamics of bacteriophage. Building on this momentum, this symposium will bring early career scientists and established investigators together in dialogue to shed light on how phage-bacteria interactions at cellular scales impact population and (co)evolutionary dynamics. In doing so, the symposium will also raise challenges for the development of theory to explore a continuum of interaction modes spanning antagonistic to mutualistic and to connect principles of near-term replication dynamics with long-term evolution.

Antoni Luque

University of Miami

"Impact and prediction of phage decay in natural microbial communities"

Phage decay is a key factor in the ecology and evolution of phages and their bacterial hosts. However, estimating the phage decay of different viruses in a community remains challenging. In this talk, I will share the approach that my lab is developing to address this problem. It relies on three complementary strategies. First, I will introduce a new transient dynamic method that facilitates identifying when phage decay and other processes are relevant in the community and under what circumstances a tipping point is expected to occur and significantly impact the community’s dynamics. Second, I will share the multiscale methods we are integrating to obtain phage decay rates for different phages from genomic data. This step relies strongly on the ability to identify structural proteins in metagenomes and the combination of several biophysical models. Third, I will show our initial attempts to relate our modeling approaches to phage decay experiments from aquatic environmental communities. I will conclude by emphasizing how the strategies discussed here could be valuable for other viruses and for optimizing phage biotechnological applications.

Asher Leeks

University of British Columbia

"Modelling the dynamics of cheating in natural populations of filamentous phages"

Diverse species of filamentous phages are found across natural environments, often encoding bacterial virulence traits, antimicrobial resistance, and novel metabolic capacity. In the laboratory, filamentous phages are vulnerable to cheating: mutants spontaneously emerge which have deleted shared gene products, and as a result can out-replicate full-length cooperative phages in coinfection. If these cheat mutants also emerge and spread in natural filamentous phage populations, this would have profound consequences for our understanding of phage population dynamics, and the dependent ecological and pathogenic consequences. However, it is difficult to detect cheating in natural populations for two key reasons: we lack longitudinal data, and so cannot directly measure the fitness of putative cheats; and most filamentous phage species are known only from sequence data, hence we cannot predict a priori which genes might have been deleted by cheats. Here, we use a quantitative approach to overcome these limitations, in order to measure cheating in natural filamentous phage populations. We construct a birth-death model that incorporates mutation, demographic noise, and a frequency-dependent selective advantage to cheating. We explicitly model the distribution of genome lengths expected under different dynamical regimes possible in the model, showing that the selective advantage to cheating can be quantified without requiring longitudinal data, analogous to signatures of selection commonly used in population genetics. This approach allows us to identify which environments allow cheats to spread, which genes are cheated across uncharacterised filamentous species, and to explore the demographic consequences of cheating for natural filamentous phage populations.

Jaye Sudweeks

University of British Columbia

"Environmental feedback can maintain cooperation in phages"

The evolution and maintenance of cooperation is a fundamental problem in evolutionary biology. Because cooperative behaviors impose a cost, cooperators are vulnerable to exploitation by defectors that do not pay the cost to cooperate but still benefit from the cooperation of others. Bacteriophages exhibit cooperative and defective phenotypes in infection: during replication, phages produce essential gene products in the host cell environment. Coinfection between multiple phages is possible, so if a phage cannot guarantee exclusive access to its own gene products, the products act as a public good; cooperators contribute to the common pool while defectors contribute less and instead appropriate goods from cooperators. Defective phage phenotypes experience negative frequency dependence in coinfection. For some phages, negative frequency dependence is strong enough to maintain the cooperative phenotype. For other phages, negative frequency dependence alone is not sufficient to maintain the cooperative phenotype, in which case the fate of cooperation is unclear. Here we propose that if coinfection is not enforced, and host and viral densities can vary, environmental feedback can maintain cooperation in such phage populations by modulating the rate of co-infection and shifting the advantages of cooperation versus defection. We build and analyze an ODE model and find that for a wide range of parameter values, environmental feedback maintains cooperation.

Nanami Kubota

University of Pittsburgh

"Cheater phages drive bacterial and phage populations to lower fitness"

How can a less reproductively fit antagonist invade a seemingly fitter population? In this study, we can partially explain such a paradox in the context of Pseudomonas phages and game theory. 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 facilitate extreme phage production, slowing bacterial growth and increasing cell death, violating an apparent détente between bacterium and phage. Furthermore, high intracellular phage replication enables another evolutionary conflict: “cheater miniphages” lacking capsid genes invade populations of full-length phages within cells. Despite the lower absolute fitness of the pf5r bacteria, bacteria carrying both hyperactive full-length phages and miniphages outcompete the wildtype bacteria in direct competition. Surprisingly, infection by both full-length phages and miniphages can shift games between infected bacteria and naïve, uninfected cells to prisoner’s dilemma, undermining coexistence. Finally, although bacteria containing full-length phages and miniphages are most immune to superinfection by limiting the Pf receptor, this hybrid is extremely unstable, as a classic Tragedy of the Commons scenario results in complete prophage loss. The entire cycle–from phage hyperactivation to miniphage invasion to prophage loss–can occur within 24 hours, 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 Pf phages in a runaway process that reduces the fitness of both host and virus.

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Annual Meeting for the Society for Mathematical Biology, 2025.