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Characterization of phage-antibiotic interaction through different in vitro methods: case study of a vibriophage

Preprint Created on 28 May 2026 bioRxiv

Climate change and warmer oceans will amplify the impacts on public health of waterborne harmful microorganisms. Phagotherapy offers a promising alternative; but as of today, phages can only be administered to patients when delivered along with antibiotics. Understanding possible interactions between these agents - indifference, synergy or antagonism - is thus a pivotal point. While several methods exist for characterizing such interaction, consensus on a reference method is still lacking. In this work, we screen and compare several in vitro characterization methods, using as a model nt-1, a phage of Vibrio natriegens, and studying its interaction with cefotaxime, a 3G cephalosporine. The different methods highlight different aspects of the interaction, depending whether they focus on phage or bacterial biomass. Overall, we see evidence of antagonism between the studied phage and antibiotic: this antagonism is at its optimum for antibiotic concentration of minimum inhibitory concentration (MIC)/2. Given the non-linear nature of interaction, it appears essential to use multiplexed methods and to cross technics.

Archambeaud, B., Douarre, C., Marcoux, P. R.

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