PhREEPred

PhREEPred predicts the emergence of phage-resistant bacterial variants during phage therapy against encapsulated pathogens such as Klebsiella pneumoniae to inform phage cocktail and depolymerase composition.

Key Features:

• Predictive Modeling: Employs a mathematical model simulating bacterial–phage population dynamics that includes bacterial growth rate, initial density, multiplicity of infection, phage latent period, infectiveness, and cocktail composition, and incorporates initial concentration and activity rate of depolymerases.
• Customizable Simulations: Accepts scenario-specific input conditions representing experimental or clinical parameters to generate tailored predictions of resistance emergence.
• Depolymerase Integration: Models the effect of capsule depolymerases, including recombinant KP34p57, in exposing alternative receptors for initially inactive phages and in delaying or preventing bacterial resistance.
• Sequential vs. Parallel Infection Analysis: Compares sequential and parallel phage infection dynamics and indicates that cocktails of sequentially infecting phages are more effective than parallel infections.

Scientific Applications:

• Phage cocktail and depolymerase design: Informs composition and sequencing of phage cocktails and phage–depolymerase combinations to combat encapsulated bacterial pathogens such as Klebsiella pneumoniae.
• Resistance emergence prediction: Predicts timing and likelihood of resistant variant emergence to support optimization of treatment composition and reduce the probability of therapeutic failure due to resistant strains.

Methodology:

Based on a mathematical model calibrated and validated with experimental data from Klebsiella pneumoniae treated with lytic phages KP34, KP15, KP27 and the recombinant capsule depolymerase KP34p57.