Synergistic Interactions between Host Immunity, Phage and Commensal Bacteria in Controlling Bacterial Pathogens

The host immune system is a critical driver of within-host dynamics of pathogens. However, there is limited understanding of the tripartite interactions between host immunity, pathogenic bacteria and antimicrobials. Combining nonlinear dynamic models and animal experiments, we have recently shown how host immunity can clear an acute respiratory infection in synergy with phage (viruses that exclusively infect bacteria) [1, 2]. As a consequence of this synergy, phage and host immunity can eliminate multidrug-resistant bacterial pathogens, even when neither phage nor the immune response can do so alone. Here, we extend our theoretical framework to include potential synergies between host immunity and commensal or probiotic bacteria. By incorporating competition between commensal and pathogenic bacteria, our results suggest that host immunity can act synergistically with commensals to eliminate bacterial pathogens by tipping the balance between beneficial and pathogenic bacterial populations. We will discuss the implications of our results for phage and probiotic therapies.

[1] D. R. Roach and C. Y. Leung et al., Cell Host Microbe 22, 38 (2017).
[2] C. Y Leung and J. S. Weitz, J. Theor. Biol. 429, 241 (2017).