Tradeoffs Between Evolved Phage Resistance and Antibiotic Susceptibility in a Highly Drug-Resistant Cystic Fibrosis-Derived Pseudomonas aeruginosa Strain

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Abstract
Background: Multi-drug resistant pathogens pose significant challenges towards the effective resolution of bacterial infections. A promising alternative strategy is phage therapy in which limited applications has afforded lifesaving resolution from drug resistant pathogens. However, adoption of this strategy is hampered by narrow bacteriophage host ranges, and as with antibiotics, bacteria can acquire resistance to phage. Methods: To address these issues, we isolated 25 broad-host range phages against multiple cystic fibrosis (CF)-derived P. aeruginosa clinical strains thus promoting their application against conspecific pathogens. To investigate evolved resistance to phage in relation to antibiotic resistance, one CF-derived P. aeruginosa strain was exposed to a lytic phage over a short time scale. Results: Trade-offs were observed in which evolved phage resistant P. aeruginosa strains showed decreased resistance to antibiotics. These traits that likely reflect single nucleotide polymorphisms. Conclusion: Results suggest phage and antibiotics may be a combined approach to treat bacterial infections.

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