Abstract

The rise of antibiotic-resistant bacterial pathogens has renewed interest in bacteriophage (phage) therapy as a potential alternative treatment. However, the evolutionary interplay between phage resistance and antibiotic susceptibility remains poorly understood, particularly in Pseudomonas species. This study investigates how phage resistance in Pseudomonas chlororaphis, a less virulent relative of P. aeruginosa, influences susceptibility to the folate pathway inhibitor trimethoprim. We hypothesized that phage-resistant mutants would exhibit altered trimethoprim sensitivity due to pleiotropic effects on efflux pumps, cell envelope structures, or biofilm formation. Using the ancestral P. chlororaphis strain (14b11), we generated phage-resistant mutants and assessed their minimum inhibitory concentration (MIC) for trimethoprim. Most mutants showed reduced growth at sub-MIC trimethoprim concentrations compared to the ancestral strain, suggesting increased susceptibility. However, some mutants displayed variable responses, indicating possible divergent resistance mechanisms. These findings suggest that phage resistance may incur fitness trade-offs affecting antibiotic susceptibility and highlight the potential for combined phage-antibiotic therapies. Given the genetic overlap between P. chlororaphis and P. aeruginosa, these results offer a safer framework for preclinical exploration and highlight the need for future molecular investigations.

Advisor

Strand, Stephanie

Department

Biology

Disciplines

Bacteriology | Pathogenic Microbiology | Pharmacology | Virology

Publication Date

2025

Degree Granted

Bachelor of Arts

Document Type

Senior Independent Study Thesis

Available for download on Sunday, July 07, 2030

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© Copyright 2025 Rithik Raj