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This content will become publicly available on November 5, 2025

Title: Leveraging mathematical modeling framework to guide regimen strategy for phage therapy
Bacteriophage (phage) cocktail therapy has been relied upon more and more to treat antibiotic-resistant infections. Understanding of the complex kinetics between phages, target bacteria, and the emergence of phage resistance remain hurdles to successful clinical outcomes. Building upon previous mathematical concepts, we develop biologically-motivated nonlinear ordinary differential equation models to explore single, cocktail, and sequential phage treatment modalities. While the optimal pairwise phage treatment strategy was the double simultaneous administration of two highly potent and asymmetrically binding phage strains, it appears unable to prevent the evolution of resistance. This treatment regimen did have a greater lysis efficiency, promoted higher phage population sizes, reduced bacterial density the most, and suppressed the evolution of resistance the longest compared to all other treatments strategies tested. Conversely, the combination of phages with polar potencies allows the more efficiently replicating phages to monopolize susceptible host cells, thereby quickly negating the intended compounding effect of cocktails. Together, we demonstrate that a biologically-motivated modeling-based framework can be leveraged to quantify the effects of each phage’s properties to more precisely predict treatment responses.  more » « less
Award ID(s):
2316631
PAR ID:
10634344
Author(s) / Creator(s):
; ; ; ; ; ; ;
Editor(s):
Kim, Jaehee
Publisher / Repository:
Open Access
Date Published:
Journal Name:
PLOS Complex Systems
Volume:
1
Issue:
3
ISSN:
2837-8830
Page Range / eLocation ID:
e0000015
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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