Electrochemical Strategy for Eradicating Fluconazole-Tolerant Candida albicans Using Implantable Titanium

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.

Antifungal Activity, Synergism with Fluconazole or Amphotericin B and Potential Mechanism of Direct Current against Candida albicans Biofilms and Persisters

“…Moreover, the protein content and extracellular conductivity rose with increasing treatment time, indicating that membrane permeability increased following DC stimulation. The increased cellular membrane permeability is able to enhance drug uptake and promote drug delivery and treatment efficacy [ 17 , 30 , 34 ]. Rh6G was used as a tracer of FLC to detect the intracellular FLC concentration, recording the changes in uptake and efflux transport of FLC [ 27 ].…”

“…The disruption of membrane integrity as well as the generation of chlorine, hypochlorous acid, oxygen and reactive oxygen species (ROS) may play an important role in the DC-induced killing effect [ 14 , 16 ]. Currently, neither the antifungal effect of DC nor its synergistic effect with antifungals on C. albicans biofilms/persisters are well-studied, and the underlying mechanisms are largely unknown [ 17 ]. The application of DC provides a promising approach to control biofilms that display increased resistance [ 12 , 18 ].…”

Advanced Electrochemical Reamer (EC-Reamer) for Root Canal Treatment

“…Introducing electrochemical treatment to the current RCT procedure will potentially help to eliminate microorganisms inside the canal system. ( 24 , 29 , 32 ). The present in vitro study guarantees 99.99% bacterial eradication in 3 seconds.…”

“…Also, conventional treatment methods such as antibiotic treatments might not be sufficient to reduce the chances of infections due to the development of various antibiotic-resistant bacteria. While various treatment methods have been reported for treating infections in medical devices or implants ( 19 , 20 ), eradicating microbial pathogens using low-level current or potential is useful where conductive materials are in place for medical treatments ( 21 – 24 ).…”