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Efflux, Signaling and Warfare in a Polymicrobial World
Ay'sha Moore-Machacek1, Antje Gloe1,2, Niall O'Leary1
1School of Microbiology, University College Cork, T12 K8AF Cork, Ireland.
Antibiotics (Basel, Switzerland)
|April 28, 2023
Summary
Antimicrobial resistance is rising, but new antibiotics are scarce. Microbial communities offer novel solutions, with efflux inhibitors showing broad anti-infective potential beyond just targeting antibiotic resistance.
Area of Science:
- Microbiology and Infectious Diseases
- Drug Discovery and Development
- Ecological Microbiology
Background:
- A critical gap exists in antimicrobial drug discovery, coinciding with a global rise in antimicrobial resistance.
- Current antibiotic development primarily yields derivatives of existing classes, often susceptible to pre-existing resistance.
- The 'perfect storm' describes the convergence of rising resistance and a dwindling antibiotic pipeline.
Purpose of the Study:
- To explore novel anti-infective strategies derived from microbial ecological interactions.
- To investigate the potential of small molecule efflux inhibitors as broad-spectrum anti-infective agents.
- To understand the role of efflux pumps in microbial physiology, virulence, and community behavior.
Main Methods:
- Examined microbial ecological perspectives for pathogen control mechanisms.
- Investigated small molecule efflux inhibitors targeting bacterial and fungal efflux pumps.
- Analyzed the role of efflux in biofilm formation, toxin transport, and stress responses within polymicrobial communities.
Main Results:
- Microbial communities possess inherent small molecule capabilities for pathogen control.
- Efflux inhibitors directly combat antibiotic efflux, a key resistance mechanism.
- Efflux inhibitors demonstrate broader anti-infective capabilities by impacting virulence factors and physiological processes.
Conclusions:
- Small molecule efflux inhibitors represent a promising avenue for novel anti-infective therapies.
- Understanding efflux mechanisms in complex microbial communities is crucial for harnessing their full therapeutic potential.
- This approach offers a paradigm shift from traditional antibiotic development, leveraging natural microbial defense strategies.
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