Within-host mathematical modeling of antibiotic-phage treatments on
lysogenic and non-lysogenic bacteria dynamics
Abstract
Bacteriophages, or phages (viruses of bacteria), play significant roles
in shaping the diversity of bacterial communities within the human gut.
A phage-infected bacterial cell can either immediately undergo lysis
(virulent/lytic infection) or enter a stable state within the host as a
prophage (lysogeny) until a trigger event, called prophage induction,
initiates the lysis process. We develop an approach based on a model
structured in terms of time since bacterial infection. We derive
important threshold parameters for the asymptotic dynamics of the system
and demonstrate that the model’s qualitative behavior can range from the
extinction of all bacterial strains to the persistence of a single
strain (either lysogen or non-lysogen bacteria) or the coexistence of
all strains at a positive steady state. We highlight the existence of
critical induction rate values that lead to the coexistence of all
states through periodic oscillations. We also conduct a global
sensitivity analysis for an effective bacterial clearance. In scenarios
where antibiotics are not sufficiently effective, we identify four key
phage parameter traits: (i) the phage induction probability, describing
the capacity of prophages to be induced, (ii) the probability of
absorption, describing the phages’ ability to invade susceptible
bacteria, (iii) the reproduction number of susceptible bacteria in the
absence of antibiotics, and (iv) the latent period, describing the time
since absorption. The obtained results emphasize the effective
therapeutic potential of selected phages.