Rule-based simulation of temperate bacteriophage infection: restriction-modification as a limiter to infection in bacterial populations.

An individual-based model (IbM) for bacterial adaptation and evolution, COSMIC-Rules, has been employed to simulate interactions of virtual temperate bacteriophages (phages) and their bacterial hosts. Outcomes of infection mimic those of a phage such as lambda, which can enter either the lytic or lysogenic cycle, depending on the nutritional status of the host. Infection of different hosts possessing differing restriction and modification systems is also simulated. Phages restricted upon infection of one restricting host can be adapted (by host-controlled modification of the phage genome) and subsequently propagate with full efficiency on this host. However, such ability is lost if the progeny phages are passaged through a new host with a different restriction and modification system before attempted re-infection of the original restrictive host. The simulations show that adaptation and re-adaptation to a particular host-controlled restriction and modification system result in lower efficiency and delayed lysis of bacterial cells compared with infection of non-restricting host bacteria. Such biologically realistic simulations validate the use of the IbM approach to predicting behaviour of bacteriophages in bacterial populations. The applicability of the model for more complex scenarios aimed at predictive modelling of bacterial evolution in a changing environment and the implications for the spread of viruses in a wider context are discussed.