Antibiotic drugs and Bacteriophages: Are they synergistic or antagonistic?

It's a dream of very many scientists especially those working in antimicrobial resistance to get the best weapon against superbugs (multidrug-resistant strains of bacteria). In the meantime the main puzzle was if the phages alone are competent enough to be used for treatment, keeping in mind that there were some negative characters that were holding back phage therapy regardless of its efficiency. While on the side of antibiotics, the world is experiencing growing resistance and a high level of toxicity once a higher concentration is used for treatment. Testing for a combined action between an antibiotic and a bacteriophage has been a theme for many researchers, with the main aim of producing the best weapon that is capable of clearing bugs with minimum side effects to the host. But the main question remained as are they antagonistic or synergistic?
The black circle indicates that a variety of phages form a phage cocktail. The red circle indicates the specific lysis of bacteria by phage-derived enzymes. The green circle represents the synergy between phages and antibiotics. The yellow circle represents phage engineering. The blue circle indicates that the phage delivers the clustered regularly interspaced short palindromic repeats-associated (CRISPR-Cas) system to eliminate host cells. Photo by Wei et al (2020)

Antagonism and synergism

Antagonism is an interaction between two or more drugs that have opposite effects on the body. Drug antagonism may block or reduce the effectiveness of one or more of the drugs. So in this case the antagonism will be between a phage preparation and a drug. while Synergism is an interaction between two or more drugs that causes the total effect of the drugs to be greater than the sum of the individual effects of each drug. Sometimes a synergistic effect can be harmful.

Is phage-antibiotics interaction synergistic or antagonistic?

Most phage antibiotics related studies reported the synergistic effects that are observed as a result of mixing phage and antibiotics. Under certain conditions, phages provide an adjuvating effect by lowering the Minimum inhibitory concentration (MIC) for drug-resistant strains. However, antagonism between phage and antibiotics has also been reported in some studies.
Furthermore, synergistic and antagonistic interactions are highly dependent on the mechanism of bacterial inhibition by the class of antibiotics paired to the phage, and when synergism is observed, it suppresses the emergence of resistant cells. Different bacteriophages show the different synergisms effects on the antibiotic.

Effects of antibiotics on phages

The determinant of how phages will get affected by the drug depends on how the drug works. Antibiotics have different modes of actions, some antibiotics are capable of causing harm to the viral particle i.e phages while others do the opposite. Before therapy scientists carry out laboratory studies to ensure the resulted effects of the combination will be synergistic.

Advantages of Phage-Antibiotics synergism

  • Reduce the potential toxicity concentration of an antibiotic
  • Minimize setbacks of phage therapy
  • Increase the chance of bacteria being responsive to the treatment
  • Phage can also act as an "adjuvant"
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Phage-antibiotic synergy (PAS) is defined as the phenomenon whereby sub-lethal concentrations of certain antibiotics can substantially stimulate the host bacteria's production of virulent phage. Phage-antibiotic synergism offers a possible opportunity for developing treatment strategies for infections caused by troublesome bacteria.

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