Abstract
Bacteria and their viral pathogens face a constant pressure for augmented immune and infective capabilities respectively. Under this reciprocally imposed selective regime we expect to see a runaway evolutionary arms race that ultimately leads to the extinction of bacteriophages, either due to immunity making their host inaccessible or the loss of their host due to exhaustion of susceptible subpopulations. Despite this prediction, in many systems host and phage coexist with minimal coevolution. Previous work explained this puzzling phenomenon by invoking spatial structure or fitness tradeoffs, which can drive coexistence and the diminishment of an arms race dynamic. However, these explanations do not apply to all systems. Here we propose a new hypothesis, that the regular loss of immunity by the bacterial host can also produce robust host-phage coexistence. We pair a general model of immunity with an experimental and theoretical case study of the CRISPR-Cas immune system to characterize and contrast the behavior of tradeoff and loss mechanisms in well-mixed systems. We find that, while both a cost of immunity and the loss of immunity can lead to stable coexistence, only a loss mechanism can do so robustly within a realistic region of parameter space.
Author Summary Bacteria in natural environments must deal with the constant threat of infection by bacteriophages (i.e., viruses that infect bacteria). This creates a situation in which bacteria that are able to develop defense against these “phages”, generally via novel mutations, have a selective advantage in the population and may rise to dominance. This rise of resistant mutants in turn puts pressure on phages so that mutations allowing phages to maintain infectivity will spread through the phage population. In this coevolutionary arms race bacteria and phages each trade mutations in an escalating battle to expand their range of resistance and infectivity respectively. Theory predicts that such arms races are unsustainable in the long term. Thus it is unclear what environmental conditions and characteristics of bacteria and phages can lead to the long-term coexistence of both parties. Here we draw into question the generality of past explanations that applied a cost in terms of growth rate to resistant bacterial strains.
We propose additionally that if bacterial defense fails or is lost at a sufficiently high rate this can produce long-term coexistence. Furthermore, this loss-driven coexistence is not sensitive to perturbations of the system.
Footnotes
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