Emergence of increased frequency and severity of multiple infections by viruses due to spatial clustering of hosts

Abstract

Multiple virus particles can infect a target host cell. Such multiple infections (MIs) have significant and varied ecological and evolutionary consequences for both virus and host populations. Yet, the in situ rates and drivers of MIs in virus-microbe systems remain largely unknown. Here, we develop an individual-based model (IBM) of virus-microbe dynamics to probe how spatial interactions drive the frequency and nature of MIs. In our IBMs, we identify increasingly spatially correlated clusters of viruses given sufficient decreases in viral movement. We also identify increasingly spatially correlated clusters of viruses and clusters of hosts given sufficient increases in viral infectivity. The emergence of clusters is associated with an increase in multiply infected hosts as compared to expectations from an analogous mean field model. We also observe long-tails in the distribution of the multiplicity of infection in contrast to mean field expectations that such events are exponentially rare. We show that increases in both the frequency and severity of MIs occur when viruses invade a cluster of uninfected microbes. We contend that population-scale enhancement of MI arises from an aggregate of invasion dynamics over a distribution of microbe cluster sizes. Our work highlights the need to consider spatially explicit interactions as a potentially key driver underlying the ecology and evolution of virus-microbe communities.

Phage-Bacterial Dynamics with Spatial Structure: Self Organization around Phage Sinks Can Promote Increased Cell Densities

“…However, this spatial variation arises, reproduction of phage and bacteria enhances that variation, whereas diffusion diminishes it. Structure leads to expanding concentrations of bacteria (colonies) and to high concentrations of phages near bacterial clusters that have been invaded [ 16 , 17 , 18 ]. The spatial variation in abundance will interact with any of several factors that could be contributors to the long-term co-maintenance of sensitive bacteria and lytic phages, as follows.…”

“… Co-infection and superinfection . Phage growth with spatial structure will often concentrate phages around cells, which for many phages will lead to high numbers of phages infecting the same cell [ 18 ]. This property will reduce the effective number of phage progeny and may allow cells to reach higher densities than in liquid.…”

Sustainability of spatially distributed bacteria-phage systems

“…The spatial heterogeneity is in part generated by the diversity of the microbial world 6 , in part by clusters of food sources, and in part caused by the fact that bacterial division leaves the offspring close to their "mother" and often lead to the formation of microcolonies [7][8][9] . The spatial heterogeneity may, in turn, amplify itself through the propagation of host-specific phages, if these percolate devastating infections through the parts of space with the most homogeneous distribution of their hosts 10 .…”

“…A typical method for introducing space in bacteria-phage modelling is by the use of cellular automata models 10,[28][29][30][31] . By utilizing a combination of lattices and diffusion of nutrient and phages, these models are used to study the interface between bacteria and phages in highly structured environments and have successfully addressed the importance of the spatial structures in various scenarios.…”

“…By utilizing a combination of lattices and diffusion of nutrient and phages, these models are used to study the interface between bacteria and phages in highly structured environments and have successfully addressed the importance of the spatial structures in various scenarios. However, many of them assume that one lattice site can contain at most one unit of bacteria, and only the bacteria adjacent to empty sites can replicate, limiting the growth to the surface of a cluster of bacteria 10,[28][29][30][31] . This can be justified if one lattice site represents a cluster of cells that is enough to deplete the resource before it diffuses to the neighbouring sites.…”