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Phages connect the biological dots of antimicrobial resistance: from genesis and spread to alternative treatment
Cleo Anastassopoulou1, Antonios-Periklis Panagiotopoulos1, Stefanos Ferous1
1Department of Microbiology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, Athens 11527, Greece.
Abstract:
Antimicrobial resistance (AMR) poses a severe global health threat, necessitating alternatives to conventional antibiotics, which are increasingly ineffective. Phages play a dual role in both propagating and potentially mitigating AMR. They facilitate AMR dissemination primarily through transduction, with emerging evidence suggesting indirect involvement in conjugation and transformation. Phage-plasmids, a dynamic entity bridging phages and plasmids, have gained increasing attention for their role in AMR evolution. Conversely, phage therapy has demonstrated promise in targeting MDR pathogens and disrupting biofilms through lytic activity and enzymatic degradation. However, challenges, such as phage resistance, host specificity and regulatory constraints, must be addressed to enable widespread clinical implementation. While regulatory frameworks for phage therapy remain underdeveloped in many regions, initiatives such as the EMA workshop in 2015 have sought to establish pathways for regulatory approval, addressing issues related to phage standardization, phage production, quality control, clinical validation and product monitoring. Leveraging the extensive experience of Eastern European countries, where phage therapy has been successfully integrated into medical practice, may accelerate its acceptance in Western healthcare systems. Integrating phages with existing antimicrobial strategies may provide a viable approach to combating AMR. Phages thus connect the biological dots of AMR by contributing to its generation and spread, but possibly also to its resolution, likely in combination with antibiotics.
Insights
Antimicrobial resistance (AMR) is a global threat. Bacteriophages (phages) can both spread and combat AMR, offering a promising therapeutic alternative when combined with antibiotics.
Area of Science:
- Microbiology
- Genetics
- Public Health
Background:
- Antimicrobial resistance (AMR) presents a critical global health challenge, driving the need for novel therapeutic strategies beyond conventional antibiotics.
- Bacteriophages (phages) exhibit a complex relationship with AMR, acting as both facilitators of resistance gene spread and potential agents for therapeutic intervention.
- Phage-plasmids represent a significant area of interest in understanding AMR evolution and phage-mediated resistance mechanisms.
Purpose of the Study:
- To explore the multifaceted role of phages in the context of antimicrobial resistance (AMR).
- To evaluate the potential of phage therapy as an alternative treatment for multidrug-resistant (MDR) pathogens and biofilms.
- To identify challenges and propose strategies for the clinical implementation of phage therapy, including regulatory considerations.
Main Methods:
- Review of existing literature on phage-bacterial interactions and AMR.
- Analysis of phage mechanisms in AMR dissemination (transduction, conjugation, transformation).
- Assessment of phage therapy applications, including lytic activity and enzymatic degradation of pathogens and biofilms.
Main Results:
- Phages contribute to AMR spread via transduction and potentially other mechanisms, with phage-plasmids playing a key role in resistance evolution.
- Phage therapy shows promise against MDR pathogens and biofilms, but faces hurdles like phage resistance and host specificity.
- Regulatory frameworks for phage therapy are evolving, with lessons learned from Eastern European countries offering valuable insights.
Conclusions:
- Phages are integral to the complex biology of AMR, influencing both its development and potential resolution.
- Phage therapy, particularly when integrated with existing antimicrobial approaches, represents a viable strategy to combat AMR.
- Addressing regulatory and practical challenges is crucial for the widespread clinical adoption of phage therapy.
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