Mole Self-grip Wrench

Abstract

<h3>Abstract</h3> Encounters among bacteria and their viral predators (bacteriophages) are among the most common ecological interactions on Earth. Further, these encounters are likely to occur predominantly within surface-bound communities that microbes most often occupy in natural environments. These communities, termed biofilms, are spatially constrained such that interactions become limited to near neighbors; diffusion of solutes and particulates is reduced; and there is pronounced heterogeneity in nutrient access and physiological state. It is appreciated from prior, abstracted theory that phage-bacteria interactions are fundamentally different in spatially structured contexts, as opposed to well-mixed liquid culture. Spatially structured communities are predicted to promote the protection of susceptible host cells from phage exposure, and thus weaken selection for phage resistance. The details and generality of this prediction in realistic biofilm environments, however, are not known. Here we explore phage-host interactions using experiments and simulations that are tuned to represent the essential elements of biofilm communities. Our simulations show that in biofilms, the coexistence of susceptible and phage-resistant bacteria is highly robust to a large array of conditions, including background growth rate, cost of phage resistance, mechanism of phage resistance, and phage diffusivity. We characterize the population dynamics underlying this coexistence, and we show that coexistence is recapitulated in an experimental model of biofilm growth measured with confocal microscopy. Our results provide a clear view into the dynamics of phage-resistance in biofilms, with single-cell resolution of the underlying cell-virion interactions, linking the predictions of canonical theory to realistic models and <i>in vitro</i> experiments of biofilm growth. <h3>Importance</h3> In the natural environment, bacteria most often live in communities bound to one another by secreted adhesives. These communities, or biofilms, play a central role in biogeochemical cycling, microbiome functioning, wastewater treatment, and disease. Wherever there are bacteria, there are also viruses that attack them, called phages. Interactions between bacteria and phages are likely to occur ubiquitously in biofilms. We show here, using simulations and experiments, that biofilms will almost universally allow phage-susceptible bacteria to be protected from phage exposure, if they are growing alongside other cells that are phage-resistant. This result has implications for the fundamental ecology of phage-bacterial interactions, as well as the development of phage-based antimicrobial therapeutics.