11 major claims checked against the paper's own evidence: 1 not fully backed by the presented evidence (unsupported or overstated).
unsupportedDiscussion, paragraph 5Reviewers 1, 2, 3
Plasmid-dependent phages can be used as a capture reagent for rare and costly plasmids.
The paper suggests this application in the Discussion (paragraph 5) but does not provide any modeling or data to support it. The claim is a speculative proposal, not backed by evidence in this study.
Evidence: None. The idea is described in a few sentences with references to existing methods, but no simulation or analysis is presented.
“Plasmid-dependent phages can be used as a capture reagent for rare and costly plasmids, which we discuss next.”
partialAbstract, ResultsReviewers 1, 3
The results are robust within realistic parameter ranges.
Parameter sweeps are shown for key variables (conjugation rate, loss probability, phage infectivity), but the paper does not systematically explore all parameter uncertainties (e.g., carrying capacity, growth rates, degradation rates). The robustness claim is partially supported.
Evidence: Figures 1D, 2G, and supplemental figures show variation over several orders of magnitude for selected parameters, but a formal sensitivity analysis is not performed.
“Our results are robust within realistic parameter ranges and yield several testable predictions.”
partialDiscussion, paragraph 4Reviewer 2
High-cost plasmids (~50% growth costs or even more) can exist in nature where plasmid-dependent phages are found.
The paper provides theoretical evidence (Figures 2 and 3) that phages can sustain a costly plasmid in silico, but does not present direct observational evidence from natural communities. The claim is stated as a testable prediction, which is appropriate.
Evidence: The prediction is listed in the Discussion; no field data are presented.
“High-cost plasmids (~ 50% growth costs or even more) can exist in nature where plasmid-dependent phages are found.”
partialDiscussion, paragraph 4Reviewer 2
Introducing plasmid-dependent phages to cultures where they are absent can drive an increase in average bacterial fitness.
The model suggests that phage predation reduces the plasmid-containing fraction, which reduces the effective growth cost (Δ_eff). This is shown in silico. No experimental validation is provided, but the claim is presented as a prediction.
Evidence: Figure 2G shows reduced effective cost as κ increases.
“Introducing plasmid-dependent phages to cultures where they are absent can drive an increase in average bacterial fitness (such as growth rates), by cutting down the abundance of any costly plasmids.”
supportedAbstract, ResultsReviewer 1
Plasmid-dependent phages can enable the survival of costly plasmids by keeping them at low abundance.
The paper presents simulation results showing that with phage predation, plasmids persist for much longer than without, and the mechanism is explained through negative feedback.
Evidence: Figures 2 and 3 show that with phage infectivity above a threshold, the plasmid-containing fraction is maintained at low levels, and persistence times increase dramatically, allowing survival until a selection event.
“plasmid-dependent phages can, counterintuitively, solve this plasmid survival problem for their bacterial hosts.”
supportedResults, Figure 1Reviewer 1
Horizontal transfer and persistence mechanisms alone are unlikely to enable long-term survival of high-cost plasmids.
The model without phage shows that even with high conjugation, plasmid-immune competitors drive extinction within a few hundred hours, except for a narrow parameter region.
Evidence: Figure 1 shows that in the absence of phage, plasmid survival time is short unless conjugation and loss rates are finely balanced.
“the survival time of the plasmid is very short, except for a narrow region where the conjugation and loss probabilities are extremely finely balanced”
supportedAbstract and Results, Figure 1Reviewers 2, 3
Horizontal transfer and persistence mechanisms are alone unlikely to enable the long-term survival of high-cost plasmids.
The Results, Figure 1C–D, demonstrate that plasmid extinction occurs rapidly (within ~500 h) unless conjugation and loss rates are improbably finely balanced, supporting the claim.
Evidence: Figure 1C shows plasmid extinction trajectory; Figure 1D shows survival time is very short except for a narrow parameter region.
“horizontal transfer and persistence mechanisms are alone unlikely to enable the long-term survival of high-cost plasmids”
supportedAbstract and ResultsReviewers 2, 3
Plasmid-dependent phages can promote the long-term survival of high-cost plasmids.
The Results, Figures 2 and 3, show that with phage present, the plasmid persists at low abundance for extended periods, and in Figure 3C it survives a selection event after 10 years. The modeling evidence supports the claim.
Evidence: Figure 2D, F show sustained plasmid abundance; Figure 3C shows survival over 10 years.
“plasmid-dependent phages can promote the long-term survival of high-cost plasmids”
supportedAbstract and Results, Figure 2GReviewers 2, 3
Phage predation pins the plasmid at low but nonzero abundance, such that the plasmid cost is effectively neutralized at the population level.
Results in Figure 2G show the plasmid-containing fraction drops dramatically (to <0.1%) as phage infectivity κ increases, and the effective growth cost Δ_eff decreases. This supports the claim.
Evidence: Figure 2G: plasmid-containing fraction (orange) falls orders of magnitude; ρ (red) also decreases.
“Phage predation pins the plasmid at low but nonzero abundance, such that the plasmid cost is effectively neutralized at the population level”
supportedAbstract and Results, Figure 3CReviewer 2
When conditions change and the costly plasmid becomes beneficial, it spreads across the host population and switches to a vertical-transmission lifestyle.
Figure 3C shows that after the selection event (antibiotic addition), the plasmid-containing population spreads and the phage-infected population declines, consistent with a shift to vertical transmission. The evidence supports the claim.
Evidence: Figure 3C: plasmid trajectory (orange) rises after selection event; phage population declines.
“When conditions change and the costly plasmid becomes beneficial, it spreads across the host population and switches to a vertical-transmission lifestyle”
supportedAbstract, ResultsReviewer 3
When conditions change and the costly plasmid becomes beneficial, it spreads across the host population and switches to a vertical-transmission lifestyle until benefits again subside.
Figure 3C demonstrates this scenario: after a 10-year selection event (antibiotic), the plasmid (which was maintained at low abundance by phage) spreads to rescue the susceptible population, and the model description states that low-conjugation subpopulations dominate during the benefit period.
Evidence: Figure 3C time course, and the text describing the selection event.
“When conditions change and the costly plasmid becomes beneficial, it spreads across the host population and switches to a vertical-transmission lifestyle until benefits again subside.”