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Published on: August 19, 2021
The Current Landscape of Phage-Antibiotic Synergistic (PAS) Interactions
Brittany S I Supina1, Jonathan J Dennis1
1Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E9, Canada.
Abstract:
Background: In response to the urgent need for new antibiotics targeting high-priority MDR pathogens, bacteriophages (phages) have emerged as promising non-traditional antimicrobial agents. Phages are viruses that infect bacteria and induce cell lysis through mechanisms distinct from those of antibiotics, making them largely unaffected by most antibiotic resistance mechanisms. Importantly, phages have been shown to work cooperatively with an array of clinically useful antibiotics, and phage-antibiotic synergy (PAS) represents a sophisticated strategy that may improve treatment outcomes. However, the interactions between phages and antibiotics are diverse, ranging from synergistic to antagonistic, and understanding the mechanisms underlying these interactions is crucial for developing effective PAS treatments. In this review, we summarize the potential evolutionary and molecular mechanisms that drive PAS and the current landscape of phage-antibiotic interactions. Conclusions: Towards the development of robust PAS strategies, we review in vitro methods for assessing PAS and considerations for choosing and employing candidate phage-antibiotic combinations.
Insights
Bacteriophages (phages) offer a novel approach to combatting multidrug-resistant (MDR) pathogens. Understanding phage-antibiotic synergy (PAS) mechanisms is key to developing effective combination therapies against resistant bacteria.
Area of Science:
- Microbiology
- Infectious Diseases
- Drug Discovery
Background:
- Multidrug-resistant (MDR) pathogens pose a significant global health threat, necessitating novel therapeutic strategies.
- Bacteriophages (phages), viruses that infect bacteria, are emerging as potent antimicrobial agents due to their distinct lytic mechanisms.
- Phages are largely unaffected by antibiotic resistance mechanisms, offering a promising alternative or adjunct to conventional antibiotics.
Purpose of the Study:
- To review the evolutionary and molecular mechanisms driving phage-antibiotic synergy (PAS).
- To summarize the current understanding of interactions between phages and antibiotics.
- To explore strategies for developing effective PAS treatments against MDR pathogens.
Main Methods:
- Literature review of existing research on phage-antibiotic interactions.
- Analysis of evolutionary and molecular mechanisms underlying PAS.
- Examination of in vitro methods for assessing PAS.
Main Results:
- Phage-antibiotic interactions exhibit a spectrum from synergistic to antagonistic.
- Understanding these interactions is crucial for optimizing combination therapies.
- Phages can enhance the efficacy of existing antibiotics against resistant bacteria.
Conclusions:
- PAS is a promising strategy for improving treatment outcomes against MDR pathogens.
- Further research into the mechanisms of PAS is essential for clinical translation.
- Standardized in vitro methods are needed for evaluating phage-antibiotic combinations.
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