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Published on: July 24, 2021
Challenges and opportunities for cheat therapy in the control of bacterial infections
James Gurney1,2, Camille Simonet3, Kristofer Wollein Waldetoft1,2,4
1Center for Microbial Dynamics & Infection, Georgia Institute of Technology, Atlanta, 30332 GA, USA. jgurney7@gatech.edu.
Abstract:
Covering: 1999 to 2021Bacterial pathogens can be highly social, communicating and cooperating within multi-cellular groups to make us sick. The requirement for collective action in pathogens presents novel therapeutic avenues that seek to undermine cooperative behavior, what we call here 'cheat therapies'. We review two broad avenues of cheat therapy: first, the introduction of genetically engineered 'cheat' strains (bio-control cheats), and second the chemical induction of 'cheat' behavior in the infecting pathogens (chemical-control cheats). Both genetically engineered and chemically induced cheats can socially exploit the cooperative wildtype infection, reducing pathogen burden and the severity of disease. We review the costs and benefits of cheat therapies, highlighting advantages of evolutionary robustness and also the challenges of low to moderate efficacy, compared to conventional antibiotic treatments. We end with a summary of what we see as the most valuable next steps, focusing on adjuvant treatments and use as alternate therapies for mild, self-resolving infections - allowing the reservation of current and highly effective antibiotics for more critical patient needs.
Insights
Novel "cheat therapies" disrupt bacterial cooperation to reduce infections. These strategies, using engineered or chemically induced cheats, offer evolutionary advantages but may have moderate efficacy, suggesting use alongside other treatments.
Area of Science:
- Microbiology
- Evolutionary Biology
- Therapeutic Development
Background:
- Bacterial pathogens exhibit cooperative behaviors within multicellular groups, contributing to disease.
- This collective action presents a therapeutic target to disrupt pathogen virulence.
Purpose of the Study:
- To review "cheat therapies" that undermine bacterial cooperation.
- To explore genetically engineered (bio-control) and chemically induced (chemical-control) cheat strategies.
- To assess the benefits, drawbacks, and future directions of cheat therapies.
Main Methods:
- Review of existing literature on cheat therapies from 1999 to 2021.
- Analysis of two primary cheat therapy approaches: bio-control and chemical-control cheats.
- Evaluation of efficacy, evolutionary robustness, and potential challenges.
Main Results:
- Both bio-control and chemical-control cheats can reduce pathogen burden and disease severity by exploiting wildtype cooperation.
- Cheat therapies offer evolutionary robustness but generally present lower to moderate efficacy compared to antibiotics.
- Challenges include achieving high efficacy and potential resistance mechanisms.
Conclusions:
- Cheat therapies represent a promising alternative or adjuvant strategy for managing bacterial infections.
- Future research should focus on optimizing efficacy, potentially through adjuvant treatments.
- These therapies could reserve conventional antibiotics for more severe or critical infections.
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