A SIMPL Model of Phage-Bacteria Interactions Accounting for Mutation and Competition

Area of Science:

• Microbiology and Infectious Diseases
• Mathematical Biology and Bioinformatics
• Biotechnology and Pharmaceutical Sciences

Background:

• Pseudomonas aeruginosa is a significant cause of hospital-acquired infections, with rising antibiotic resistance necessitating alternative treatments.
• Bacteriophage therapy shows promise but requires a deeper understanding of host-phage interactions for clinical application.

Purpose of the Study:

• To develop and validate a mathematical model simulating the dynamics between Pseudomonas aeruginosa and bacteriophages.
• To provide parameter estimates for specific phage-P. aeruginosa interactions to advance phage therapy research.

Main Methods:

• A system of ordinary differential equations was employed to model bacterial (susceptible, infected, mutated) and bacteriophage populations.
• The model was fitted to experimental data obtained from a microwell setting.
• Optical density readings were analyzed to determine bacterial concentrations, accounting for cellular debris.

Main Results:

• The model successfully captured the observed dynamics between P. aeruginosa and bacteriophages.
• Unique parameter estimates were derived from experimental data fitting for a specific phage-strain combination.
• Bacterial debris from lysed cells significantly impacts optical density measurements, contributing approximately 31% of the signal from a live cell.

Conclusions:

• Mathematical modeling is a valuable tool for elucidating complex host-pathogen dynamics in bacteriophage therapy.
• The study provides essential kinetic parameters for P. aeruginosa-phage interactions.
• Accurate bacterial concentration assessment requires accounting for the optical density contribution of bacterial debris.