On the persistence of lytic bacteriophages in vivo and its consequences for bacteriophage therapy

Abstract: Bacteriophages are viruses infecting bacteria and archaea. Many phage species cause infections which lead to the certain death of the infected prokaryotic host cell and the release of a large batch of phage progeny, yet they have been able to stably coexist with their bacterial hosts over the eons in nature, as well as in the majority of laboratory experiments reported in the literature. This possibility of a stable coexistence between populations of bacteria and bacteriophages can be suspected to critically reduce the chances of a successful therapeutic application of bacteriophages for combatting pathogenic bacterial infections in vivo. Here, we extend an established differential equation model describing the interaction of bacteria, bacteriophages, and the host immune system, modelling different degrees of spatial heterogeneity of the host organism by introducing a scaling parameter which alters the encounter rates of the different cell populations. We demonstrate by rigorous mathematical analysis that, depending on the degree of spatial heterogeneity, the system will either converge to the desired state of bacterial and phage extinction, to a state of persisting bacterial infection with a completely eliminated bacteriophage population or to an equally undesirable state of a stable long-term bacteria-bacteriophage coexistence. We additionally provide numerical solutions of the model to illustrate the emerging dynamics and discuss some implications for bacteriophage therapy.