BONDAD, Sofia Danielle N.

2013-55506
MCB 102

Modelling the synergistic elimination of bacteria by phage and the innate immune system
Chung Yin (Joey) Leung , Joshua S. Weitz

(Summary)
Phage therapy has been in the works of researchers for as early as 1920s, but was set aside
due to the emergence of antibiotics. However, discoveries regarding antibiotic resistance led to the
reemerging researches on alternative ways on how to combat microbial infections, thus continuing
studies regarding phage therapy. Despite interests in the field, researchers have yet to answer basic
questions regarding the use of phages in curing microbial infections.
There have been a lot of studies in the past years of researchers figuring out how phage
therapy works. There have been in vitro experiments, such as co-existing of both bacteria and
phage that resulted to mutant bacteria having resistance to the phage. In vivo experimentation, on
the other hand, gave different results. The presence of the host’s immune system and phage,
increased the chances of effective phage therapy.
The authors (Leung and Weitz, 2017) used mathematical models to show how the host’s
innate immune system, phage, and infectious bacteria interact to each other. They created a model
that will enable synergistic elimination of infectious bacteria. The host’s immune saturation
(maximum capacity of the innate immune system to perform its function) and bacteria’s immune
evasion (mechanisms of bacteria to prevent host’s innate immune responses) were the factors
considered in the model.
As a result, they have created three classes of fixed points and its possible outcomes. The
first class has no bacteria present (also no phage present as it requires presence of bacteria) and
the presence of limited number of immune responses corresponding to its maximum capacity. In
the second class, there is also no bacteria present (phage-free), but there is insufficient number of
immune response to eliminate bacteria even at its maximum capacity. On the other hand,
coexistence of the bacteria, phage, and innate immune system is present in the third class. There
is only a successful elimination of bacteria in a class I system. In class II system, the bacteria
continued to grow due to the absence of phage, while in class III system, the combined abilities of
the immune response and phage is not enough to eradicate the amount of bacteria present.
They also compared the synergistic effects between the immune response and phage. In
the first case, the bacteria only interacted with the phage. The phage present in the system was not
able to eliminate the bacteria present. Interaction between bacteria and immune system was
observed in the second case. Growth of both bacteria and immune response was observed, but due
to the limitation of immune responses, it did not successfully eliminate the bacteria. Interaction of
phage and innate immune system was observed in case III upon presence of the infectious dose of
bacterial pathogen. Initially, phage acted upon the presence of bacteria, decreasing its virulence as
innate immune response is growing in the system. By the time the innate immune response reached
its maximum capacity, the system is already at class I fixed point where there is only a minimal
presence of bacteria, and high amount of immune response. This mechanism resulted to the
elimination of the infectious bacteria.
The study also explained the effects of both static phage-immune synergy (the phage is the
initial reactor, and not the immune system) and dynamic phage-immune synergy (immune system
is the initial reactor, and not the phage). It was stated that in either type of synergy, phage with
high effectiveness act synergistically with the innate immune system. In the static synergy, phage
will lower the bacterial count to a number that can be eliminated by the innate immune system. On
the other hand, in the dynamic synergy, immediate introduction of phage weakens the system that
can be handled by the innate immune system.

Leung, C., & Weitz, J. S. (2017). Modeling the synergistic elimination of bacteria by phage and
the innate immune system. Journal of Theoretical Biology, 429, 241-252.
doi:10.1016/j.jtbi.2017.06.037