Pyocyanin-dependent electrochemical inhibition of Pseudomonas aeruginosa biofilms is synergistic with antibiotic treatment
Abstract
Pseudomonas aeruginosa biofilms are common in chronic wound infections and recalcitrant to treatment. Survival of cells within oxygen-limited regions in these biofilms is enabled by extracellular electron transfer (EET), whereby small redox active molecules act as electron shuttles to access distal oxidants. Here, we report that electrochemically controlling the redox state of these electron shuttles, specifically pyocyanin (PYO), can impact cell survival within anaerobic P. aeruginosa biofilms and can act synergistically with antibiotic treatment. Prior results demonstrated that under anoxic conditions, an electrode poised at sufficiently oxidizing potential (+100 mV vs Ag/AgCl) promotes EET within P. aeruginosa biofilms by re-oxidizing PYO for reuse by the cells. Here, when a reducing potential (−400 mV vs Ag/AgCl) was used to disrupt PYO redox cycling by maintaining PYO in the reduced state, we observed a 100-fold decrease in colony forming units within these biofilms compared with those exposed to electrodes poised at +100 mV vs Ag/AgCl. Phenazine-deficient Δphz* biofilms were unaffected by the potential applied to the electrode but were re-sensitized by adding PYO. The effect at −400 mV was exacerbated when biofilms were treated with sub-MICs of a range of antibiotics. Most notably, addition of the aminoglycoside gentamicin in a reductive environment almost completely eradicated wild-type biofilms but had no effect on the survival of Δphz* biofilms in the absence of phenazines. These data suggest that antibiotic treatment combined with the electrochemical disruption of PYO redox cycling, either through the toxicity of accumulated reduced PYO or the disruption of EET, or both, can lead to extensive killing.
Additional Information
© 2023 Jiménez Otero et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. We thank Georgia Squyres, Richard Horak, and Jinyang Li for helpful feedback on experimental design and an earlier version of the manuscript. Support for this project was provided by a grant from the NIH to D.K.N. (1R01AI127850-01A1). The authors declare no conflict of interest.Files
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Additional details
- Eprint ID
- 121903
- DOI
- 10.1128/mbio.00702-23
- Resolver ID
- CaltechAUTHORS:20230615-473786000.3
- PMCID
- PMC10470778
- 1R01AI127850-01A1
- NIH
- Created
-
2023-06-16Created from EPrint's datestamp field
- Updated
-
2023-06-16Created from EPrint's last_modified field
- Caltech groups
- Division of Geological and Planetary Sciences, Division of Biology and Biological Engineering