Live and let die: lysis time variability and resource limitation shape lytic bacteriophage fitness
Bibliographic record
Abstract
Abstract Bacteriophages (phages) play a critical role in controlling bacterial populations, both in nature and as potential therapeutic agents. Their ability to replicate, compete against each other, and eradicate target cell populations is usually understood through a number of ‘life history parameters’, traditionally measured by population-level assays, which implicitly average the parameter’s value across a large number of infection events. Recent experiments suggest that bacteriophage life history parameters are subject to considerable heterogeneity, raising the question of whether experimental and modelling efforts that do not account for this variability may overlook important factors in phage’s behaviour, competitive fitness or therapeutic viability. Here, using agent-based simulations, we investigate the importance of stochasticity in lysis time and burst size of lytic bacteriophages in two common laboratory competition experiments: serial passage of well-mixed populations and plaque expansion across a bacterial lawn. We find that a phage’s analytic growth rate in isolation can be a poor predictor of its fitness advantage in simulated competition experiments. Specifically, when lysis times are tightly distributed, we identify a novel effect we name “population resonance”, through which a bacteriophage can display a significant fitness advantage over a competitor with a much greater growth rate in isolation. Our simulations also show that both serial passage and plaque expansion reward variability in lysis time more than expected, by increasing the phage resilience when resources are scarce. Author Summary Bacteriophages (viruses that infect bacteria) can be described by a set of attributes called ‘life history parameters’. Historically, these parameters could only be measured on-average over large populations. Recent experimental advancements, however, have enabled their quantification at the single-cell-single-virus level, and have revealed that these traits are subject to inherent variability, even for genetically identical viruses infecting genetically identical cells. Here, we explore whether the degree of variability in one particular life history parameter, the lysis time (the time taken for a bacteriophage to infect and kill its host bacteria) might be subject to natural selection, by quantifying its effects on phage’s fitness in two simulated competition experiments: serial passage and plaque expansion. Surprisingly, we find that lysis time variability is advantageous in competition even when it reduces the phage’s growth rate in isolation. This finding opens the door to future computational and experimental work, as it demonstrates that mean values alone are not sufficient to describe or predict a bacteriophage efficacy, and that models that ignore this variability can overlook viable evolutionary strategies.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".