PT - JOURNAL ARTICLE AU - Matthew Simmons AU - Matthew C. Bond AU - Britt Koskella AU - Knut Drescher AU - Vanni Bucci AU - Carey D. Nadell TI - Biofilm structure promotes coexistence of phage-resistant and phage-susceptible bacteria AID - 10.1101/552265 DP - 2019 Jan 01 TA - bioRxiv PG - 552265 4099 - http://biorxiv.org/content/early/2019/10/08/552265.short 4100 - http://biorxiv.org/content/early/2019/10/08/552265.full AB - Encounters among bacteria and their viral predators (bacteriophages) are likely among the most common ecological interactions on Earth. Phage-bacterial coevolution has received abundant theoretical and experimental attention for decades and forms an important basis for molecular genetics and theoretical ecology and evolution. However, at present, relatively little is known about the nature of phage-bacteria interaction inside the surface-bound communities that microbes often occupy in natural environments. These communities, termed biofilms, are encased in a matrix of secreted polymers produced by their microbial residents. Biofilms are spatially constrained such that interactions become limited to neighbors or near neighbors; diffusion of solutes and particulates is often reduced; and there is pronounced heterogeneity in nutrient access and therefore physiological state. These factors can dramatically impact the way phage infections proceed even in simple, single-strain biofilms. Here we investigate how biofilm-specific properties impact bacteria-phage population dynamics using a computational simulation framework customized for implementing phage infection inside biofilms containing phage-resistant and phage-susceptible bacteria. Our simulations predict that it is far more common for phage-susceptible and phage-resistant bacteria to coexist inside biofilms relative to planktonic culture, where phages and hosts are well-mixed. We characterize the population dynamic feedbacks underlying this coexistence, and we then confirm that coexistence is recapitulated in an experimental model of biofilm growth measured with confocal microscopy at single-cell resolution. Our results provide a clear view into the population dynamics of phage resistance in biofilms with microscopic resolution of the underlying cell-cell and cell-phage interactions; they also draw an analogy between phage ‘epidemics’ on the sub-millimeter scale of biofilms and the process of herd immunity studied for decades at much larger spatial scales in populations of plants and animals.