Treatment of Cancer-Associated Bacteria Using Programmed Bacteriophages and pH Modulation

This project proposes an innovative anticancer therapy approach combining genetically engineered bacteriophages with modulation of the tumor microenvironment pH to selectively eliminate cancer-associated bacteria. Key bacterial species targeted include Helicobacter pylori, Fusobacterium nucleatum, and Escherichia coli, which contribute to tumor progression and therapy resistance. Using bioinformatics tools, bacteriophages are designed with pH-sensitive genetic circuits that activate lytic functions preferentially under acidic extracellular pH conditions typical of tumor environments. Computational models simulate bacterial population dynamics following the exponential decay model: P(t) = P0 × e^(-k × t), where P(t) is the bacterial population at time t, P0 the initial population, and k the decay constant depending on phage activity and environmental pH. The project also evaluates the synergistic effect of pH modulation to enhance phage stability and bactericidal efficacy while preserving healthy tissue. Expected outcomes include theoretical elimination times of targeted bacteria, optimized phage design parameters, and a validated framework for future experimental validation. This work contributes a novel precision oncology paradigm focusing on the tumor microbiome as a therapeutic target through combined biological and microenvironmental interventions.