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Electrochemical Strategy for Eradicating Fluconazole-Tolerant Candida albicans Using Implantable Titanium
Eloise Parry-Nweye, Nna-Emeka Onukwugha, Sricharani Rao Balmuri
1Biofilm Research Laboratory, Department of Orthodontics and Divisions of Pediatric Dentistry & Community Oral Health, School of Dental Medicine , University of Pennsylvania , Philadelphia , Pennsylvania 19104 , United States.
Abstract:
A persistent problem in modern health care derives from the overwhelming presence of antibiotic-resistant microbes on biomaterials, more specifically, fungal growth on metal-based implants. This study seeks to investigate the antifungal properties of low-level electrochemical treatments delivered using titanium electrodes against Candida albicans. We show that C. albicans can be readily controlled with electrical currents/potentials, reducing the number of viable planktonic cells by 99.7% and biofilm cells by 96.0-99.99%. Additionally, this study explores the ability of the electrochemical treatments to potentiate fluconazole, a clinically used antifungal drug. We have found that electrochemical treatment substantially enhances fluconazole killing activity. While fluconazole alone exhibits a low efficiency against the stationary phase and biofilm cells of C. albicans, complete eradication corresponding to 7-log killing is achieved when the antifungal drug is provided subsequently to the electrochemical treatment. Further mechanistic analyses have revealed that the sequential treatment shows a complex multimodal action, including the disruption of cell wall integrity and permeability, impaired metabolic functions, and enhanced susceptibility to fluconazole, while altering the biofilm structure. Altogether, we have developed and optimized a new therapeutic strategy to sensitize and facilitate the eradication of fluconazole-tolerant microbes from implantable materials. This work is expected to help advance the use of electrochemical approaches in the treatment of infections caused by C. albicans in both nosocomial and clinical cases.
Insights
Electrochemical treatments effectively eliminate Candida albicans on implants, reducing fungal cells by over 99%. Combining this with fluconazole eradicates drug-resistant fungi, offering a new strategy for implant-associated infections.
Area of Science:
- Biomedical Engineering
- Infectious Diseases
- Materials Science
Background:
- Antibiotic-resistant microbes on biomaterials, particularly fungal infections like Candida albicans on metal implants, pose a significant challenge in healthcare.
- Current treatments often struggle with efficacy against sessile or stationary phase fungal cells.
Purpose of the Study:
- To investigate the antifungal efficacy of low-level electrochemical treatments against Candida albicans using titanium electrodes.
- To explore the synergistic effect of electrochemical treatment and fluconazole for enhanced fungal eradication.
Main Methods:
- Application of low-level electrical currents/potentials via titanium electrodes to cultures of Candida albicans.
- Assessment of planktonic and biofilm cell viability post-treatment.
- Evaluation of fluconazole efficacy alone and sequentially after electrochemical treatment.
- Mechanistic studies to understand treatment-induced cellular changes.
Main Results:
- Electrochemical treatment significantly reduced viable planktonic Candida albicans cells by 99.7% and biofilm cells by 96.0-99.99%.
- Sequential application of electrochemical treatment followed by fluconazole achieved complete eradication (7-log killing) of fluconazole-tolerant cells.
- Mechanistic analysis revealed disrupted cell wall integrity, impaired metabolism, and altered biofilm structure.
Conclusions:
- Low-level electrochemical treatment is a potent antifungal strategy against Candida albicans on titanium implants.
- The combination therapy demonstrates a synergistic effect, overcoming fluconazole tolerance and facilitating microbial eradication.
- This approach offers a promising new therapeutic avenue for managing implant-associated fungal infections.
