Antibiotic drugs and Bacteriophages: Are they synergistic or antagonistic?

Many scientists, particularly those working on antimicrobial resistance, wish to develop the most effective weapon against superbugs (multidrug-resistant strains of bacteria). Meanwhile, the central question was whether the phages alone were capable of being used for treatment, keeping in mind that some negative characteristics were impeding phage therapy regardless of its efficacy. When it comes to antibiotics, the world is seeing an increase in resistance as well as a high level of toxicity when a higher concentration is used for treatment. Many researchers have been testing for the combined action of an antibiotic and a bacteriophage, with the goal of producing the best weapon capable of clearing bugs with the least harm to the patient. But the main question was whether they were antagonistic or synergistic.
The black circle indicates that a phage cocktail is made up of a variety of phages. The red circle denotes specific bacterial lysis by phage-derived enzymes. The green circle depicts the interaction of phages and antibiotics. Phage engineering is represented by the yellow circle. The blue circle indicates that the phage uses the clustered regularly interspaced short palindromic repeats-associated (CRISPR-Cas) system to destroy host cells. Photo by Wei et al. (2020)

Antagonism and synergism

Antagonism is the interaction of two or more drugs with opposing effects on the body. Drug antagonism can prevent or reduce the efficacy of one or more drugs. In this case, the antagonistic relationship will be between a phage preparation and a drug. While synergism is a drug interaction that causes the total effect of the drugs to be greater than the sum of the individual effects of each drug. A synergistic effect can sometimes be harmful.

Is phage-antibiotics interaction synergistic or antagonistic?

The majority of phage antibiotics-related studies reported synergistic effects observed when phage and antibiotics were combined. Phages have an adjuvant effect under certain conditions by lowering the Minimum inhibitory concentration (MIC) for drug-resistant strains. Some studies, however, have found antagonism between phage and antibiotics.
Furthermore, synergistic and antagonistic interactions are heavily reliant on the mechanism of bacterial inhibition by the antibiotic class paired with the phage. When Synergism is observed, the emergence of resistant cells is suppressed. Different bacteriophages exhibit different antibiotic synergism effects.

Effects of antibiotics on phages

The manner in which the drug affects phages is determined by how the drug works. Antibiotics work in a variety of ways; some antibiotics can harm the viral particle, i.e., phages, while others do the opposite. Prior to therapy, scientists conduct laboratory tests to ensure that the combination's resulting effects are synergistic.

Advantages of Phage-Antibiotics synergism

  • Reduce the potential toxicity concentration of an antibiotic
  • Minimize setbacks of phage therapy
  • Increase the likelihood that bacteria will respond to the treatment.
  • The phage can also function as an "adjuvant."
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The phenomenon of phage-antibiotic synergy (PAS) is defined as the ability of sub-lethal concentrations of certain antibiotics to significantly stimulate the host bacteria's production of virulent phage. Phage-antibiotic Synergism may provide an opportunity for the development of treatment strategies for infections caused by troublesome bacteria.


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  1. Wow! great article. Thanks for sharing

  2. Worth sharing.....

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