The dynamics of phage predation on a microcolony.

Phage predation is an important factor for controlling the bacterial biomass. At face value, dense microbial habitats are expected to be vulnerable to phage epidemics due to the abundance of fresh hosts immediately next to any infected bacteria. Despite this, the bacterial microcolony is a common habitat for bacteria in nature. Here, we experimentally quantify the fate of microcolonies of Escherichia coli exposed to virulent phage T4. It has been proposed that the outer bacterial layers of the colony will shield the inner layers from the phage invasion and thereby constrain the phage to the colony's surface. We develop a dynamical model that incorporates this shielding mechanism and fit the results with experimental measurements to extract important phage-bacteria interaction parameters. The analysis suggests that, while the shielding mechanism delays phage attack, T4 phage are able to diffuse so deep into the dense bacterial environment that colony-level survival of the bacterial community is challenged.

A growing microcolony can survive and support persistent propagation of virulent phages.

Bacteria form colonies and secrete extracellular polymeric substances that surround the individual cells. These spatial structures are often associated with collaboration and quorum sensing between the bacteria. Here we investigate the mutual protection provided by spherical growth of a monoclonal colony during exposure to phages that proliferate on its surface. As a proof of concept we exposed growing colonies of Escherichia coli to a virulent mutant of phage P1. When the colony consists of less than [Formula: see text]50,000 members it is eliminated, while larger initial colonies allow long-term survival of both phage-resistant mutants and, importantly, colonies of mostly phage-sensitive members. A mathematical model predicts that colonies formed solely by phage-sensitive bacteria can survive because the growth of bacteria throughout the colony exceeds the killing of bacteria on the surface and pinpoints how the critical colony size depends on key parameters in the phage infection cycle.

On Phage Adsorption to Bacterial Chains.

Bacteria often arrange themselves in various spatial configurations, which changes how they interact with their surroundings. In this work, we investigate how the structure of the bacterial arrangements influences the adsorption of bacteriophages. We quantify how the adsorption rate scales with the number of bacteria in the arrangement and show that the adsorption rates for microcolonies (increasing with exponent ∼1/3) and bacterial chains (increasing with exponent ∼0.5-0.8) are substantially lower than for well-mixed bacteria (increasing with exponent 1). We further show that, after infection, the spatially clustered arrangements reduce the effective burst size by more than 50% and cause substantial superinfections in a very short time interval after phage lysis.

Emergence of networks of shared restriction-modification systems in phage-bacteria ecosystems.

Restriction-modification (RM) systems are the most ubiquitous bacterial defence systems against bacteriophages. Using genome sequence data, we showed that RM systems are often shared among bacterial strains in a structured way. Examining the network of interconnections between bacterial strains within genera, we found that many strains share more RM systems than expected compared with a suitable null model. We also found that many genera have a larger than expected number of bacterial strains with unique RM systems. We used population dynamics models of closed and open phage-bacteria ecosystems to qualitatively understand the selection pressures that could lead to such network structures with enhanced overlap or uniqueness. In our models, we found that the phages impose a selection pressure that favours bacteria with greater number of RM systems, and higher overlap of RM systems with other strains, but in bacteria-dominated states, this is opposed by the increased cost-to-growth rate of these bacteria. Similar to what we observed in the genome data, we found that two distinct bacterial strategies emerge - strains either have a greater overlap than expected, or, at the other extreme, have unique RM systems. The former strategy appears to dominate when the repertoire of available RM systems is smaller but the average number of RM systems per strain is larger.

Defence versus growth in a hostile world: lessons from phage and bacteria.

Bacterial communities are often highly diverse with several closely related species (or strains) coexisting together. These bacteria compete for resources and the competitive exclusion principle predicts that all but the fastest-growing bacteria will go extinct. When exposed to phage, it is predicted that bacterial strains with restriction-modification (RM) systems can circumvent the competitive exclusion principle and reach diversity of the order of the phage burst size. We show that with a trade-off between bacterial growth rates and the strength of their RM systems, the diversity of such an ecosystem can further increase several fold beyond the burst size limit. Moreover, we find that the ratio of the growth rate of a bacterial strain to the imperfection of its RM system is an excellent predictor of (i) whether the strain will go extinct or not, and (ii) the biomass of the strain if it survives. In contrast, the growth rate alone is not a determinant of either of these properties. Our work provides a quantitative example of a model ecosystem where the fitness of a species is determined not by growth rate, but by a trade-off between growth and defence against predators.

Sustainability of spatially distributed bacteria-phage systems.

Virulent phages can expose their bacterial hosts to devastating epidemics, in principle leading to complete elimination of their hosts. Although experiments indeed confirm a large reduction of susceptible bacteria, there are no reports of complete extinctions. We here address this phenomenon from the perspective of spatial organization of bacteria and how this can influence the final survival of them. By modelling the transient dynamics of bacteria and phages when they are introduced into an environment with finite resources, we quantify how time delayed lysis, the spatial separation of initial bacterial positions, and the self-protection of bacteria growing in spherical colonies favour bacterial survival. Our results suggest that spatial structures on the millimetre and submillimetre scale play an important role in maintaining microbial diversity.