Hitchhiking, collapse and contingency in phage infections of migrating bacterial populations

Abstract

Natural bacterial populations are subject to constant predation pressure by phages. Bacteria use a variety of well-studied molecular mechanisms to defend themselves from phage predation. However, since phage are non-motile, perhaps the simplest defense against phage would be for bacteria to outrun their predators. In particular, chemotaxis, the active migration of bacteria up attractant gradients, may help the bacteria escape slowly diffusing phages. Here we study phage infection dynamics in migrating bacterial populations driven by chemotaxis through low viscosity agar plates. We find that expanding phage-bacteria populations support two migrating fronts, an outermost \"bacterial\" front driven by nutrient uptake and chemotaxis and an inner \"phage\" front at which bacterial population collapses due to phage predation. We show that with increasing adsorption rate and initial phage population, the rate of migration of the phage front increases, eventually overtaking the bacterial front and driving the system across a \"phage transition\" from a regime where bacteria outrun a phage infection to one where they must evolve phage resistance to survive. We confirm experimentally that this process requires phages to \"surf\" the bacterial front by repeatedly reinfecting the fastest moving bacteria. A deterministic model recapitulates the transition. Macroscopic fluctuations in bacterial densities at the phage front suggest that a feedback mechanism, possibly due to growth rate dependent phage infection rates, drives millimeter scale spatial structure in phage-bacteria populations. Our work opens a new, spatiotemporal, line of investigation into the eco-evolutionary struggle between bacteria and their phage predators.\n\nSignificance StatementThe infection of bacteria by phage requires physical contact. This fact means that motile bacteria may avoid non-motile phage by simply running away. By this mechanism bacterial chemotaxis may help bacteria to escape phages. Here we show that when phage infect bacteria moving in soft agar plates, high phage populations or infectivity rates result in phages stopping and killing all bacteria. Conversely, when initial phage numbers or infectivity rates are low, bacteria are able to migrate away from phage successfully, despite phage ability to \"surf\" bacterial fronts for more than 24 hours. Between these regimes we document a \"phage transition\" where bacterial physiology and contingency in phage infection manifest through large-scale fluctuations in spatio-temporal dynamics.