Synergistic & Antagonistic Interactions of Phages and Two Antibiotic Classes Against Multidrug-Resistant Bacteria
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Date
2025-03
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Abstract
Introduction: The rise of antibiotic-resistant bacteria has necessitated the exploration of alternative therapeutic strategies, including the use of bacteriophages (phages) in combination with antibiotics. This study investigates the synergistic and antagonistic interactions between phages and tetracycline and fluoroquinolone class antibiotics, specifically focusing on tetracycline, doxycycline, and ciprofloxacin against multidrug resistant bacterial strains of Staphylococcus aureus.
Methods: Ciprofloxacin, Tetracycline and Doxycycline susceptibility assays are completed using minimum inhibitory concentration (MIC) tests against S. aureus isolates D712 (P3L#149) and C-62 (P3L#22). MIC tests are done based on CLSI (Clinical & Laboratory Standards Institute). A serial dilution of antibiotic concentrations is added to a 96 well plate in addition to the bacterial isolate to determine the minimum concentration of antibiotic that hinders bacterial growth. Upon determination of MIC values, modified checkerboard experiments with Sb-1 phage and the antibiotics were performed. For this purpose, 96 well plates were used with varying concentrations of antibiotic in the horizontal axis and phage concentrations in vertical axis. All susceptibility tests were performed in cation adjusted Mueller Hinton Broth (MHB). Combination synergy was defined as clearance of bacterial growth inside the MIC range.
The bacteriophage used was Sb-1 phage purchased from Eliava Phage Institute, Tblisi, Georgia. Sb-1 is a myophage categorized as Herelleviridae, GenBank accession no HQ163896
Results: Our findings suggest that the mechanism of action of tetracycline antibiotics which inhibit protein synthesis plays a crucial role in determining the nature of phage-antibiotic interactions. Despite antagonism with tetracyclines we observed synergy with ciprofloxacin. The noted differences in antagonism and synergism between the various antibiotic phage combinations against S. aureus strains highlights the importance of assessing and enhancing the efficacy of such combination therapies in treating bacterial infections in a clinical setting.
Conclusions: This research underscores the potential of phage-antibiotic combinations to overcome antibiotic resistance, highlighting the importance of selecting appropriate phage-antibiotic combinations to maximize therapeutic efficacy. Further investigation into the molecular mechanisms underlying these interactions is essential for optimizing phage therapy protocols and improving clinical outcomes in the treatment of resistant bacterial infections.
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Innovations in Medicine (The Ohio State University Denman Undergraduate Research Forum)
Keywords
Antibiotic resistance, phage therapy