Biology subjects

Gelston, S.

Publications and source records attributed to Gelston, S..

3 recordsLinked to original sources

bioRxiv2024

Evaluation of Treatment of Methicillin-Resistant Staphylococcus aureus Biofilms with Intermittent Electrochemically-Generated H2O2 or HOCl

Chronic wound infections can be difficult to treat and may lead to impaired healing and worsened patient outcomes. Novel treatment strategies are needed. This study evaluated effects of intermittently produced H2O2 and HOCl, generated via an electrochemical bandage (e-bandage), against methicillin-resistant Staphylococcus aureus biofilms in an agar membrane biofilm model. By changing the working electrode potential, the e-bandage generated either HOCl (1.5 VAg/AgCl) or H2O2 (-0.6 VAg/AgCl). The degree of biocidal activity of intermittent treatment with HOCl and H2O2 correlated with HOCl treatment time; HOCl treatment durations of 0, 1.5, 3, 4.5, and 6 hours (with the rest of the 6 hour total treatment time devoted to H2O2 generation) resulted in mean biofilm reductions of 1.36{+/-}0.2, 2.22{+/-}0.16, 3.46{+/-}0.38, 4.63{+/-}0.74 and 7.66{+/-}0.5 log CFU/cm2, respectively vs. non-polarized controls, respectively. However, application of H2O2 immediately after HOCl treatment was detrimental to biofilm removal. For example, 3-hours HOCl treatment followed by 3-hours H2O2 resulted in a 1.90{+/-}0.84 log CFU/cm2 lower mean biofilm reduction than 3-hours HOCl treatment followed by 3-hours non-polarization. HOCl generated over 3-hours exhibited biocidal activity for at least 7.5-hours after e-bandage operation ceased; 3-hours of HOCl generation followed by 7.5-hours of non-polarization resulted in a biofilm cell reduction of 7.92{+/-}0.12 log CFU/cm2 vs. non polarized controls. Finally, intermittent treatment with HOCl (i.e., interspersed with periods of e-bandage non-polarization) for various intervals showed similar effects (approximately 6 log CFU/cm2 reduction vs. non-polarized control) to continuous treatment with HOCl for 3-hours, followed by 3-hours of non-polarization. These findings suggest that timing and sequencing of HOCl and H2O2 treatments are crucial for maximizing biofilm control.

bioengineering↗

bioRxiv2024

DUAL ACTION ELECTROCHEMICAL BANDAGE OPERATED by a PROGRAMMABLE MULTIMODAL WEARABLE POTENTIOSTAT

Electrochemical bandages (e-bandages) can be applied to biofilm-infected wounds to generate reactive oxygen species, such as hypochlorous acid (HOCl) or hydrogen peroxide (H2O2). The e-bandage-generated HOCl or H2O2 kills biofilms in vitro and in infected wounds on mice. The HOCl-generating e-bandage is more active against biofilms in vitro, although this distinction is less apparent in vivo. The H2O2-generating e-bandage, more than the HOCl-generating e-bandage, is associated with improved healing of infected wounds. A strategy in which H2O2 and HOCl are generated alternately--for dual action--was explored. The goal was to develop a programmable multimodal wearable potentiostat (PMWP) that could be programmed to generate HOCl or H2O2, as needed. An ultralow-power microcontroller unit managed operation of the PMWP. The system was operated with a 260-mAh capacity coin battery and weighed 4.6 grams, making it suitable for small animal experiments or human use. The overall cost of a single wearable potentiostat was $6.50 (USD). The device was verified using established electrochemical systems and functioned comparably to a commercial potentiostat. To determine antimicrobial effectiveness, PMWP-controlled e-bandages were tested against clinical isolates of four prevalent chronic wound bacterial pathogens, methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterococcus faecium, and one fungal pathogen of emerging concern, Candida auris. PMWP-controlled e-bandages exhibited broad-spectrum activity against biofilms of all study isolates tested when programmed to deliver HOCl followed by H2O2. These results show that the PMWP operates effectively and is suitable for animal testing.

bioengineering↗

bioRxiv2024

HOCl-producing Electrochemical Bandage is Active in Murine Polymicrobial Wound Infection

Wound infections, exacerbated by the prevalence of antibiotic-resistant bacterial pathogens, necessitate innovative antimicrobial approaches. Polymicrobial infections, often involving Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA), present formidable challenges due to biofilm formation and antibiotic resistance. Hypochlorous acid (HOCl), a potent antimicrobial agent produced naturally by the immune system, holds promise as an alternative therapy. An electrochemical bandage (e-bandage) that generates HOCl in situ was evaluated for treatment of murine wound biofilm infections containing both MRSA and P. aeruginosa with "difficult-to-treat" resistance. Previously, the HOCl-producing e-bandage was shown to reduce wound biofilms containing P. aeruginosa alone. Compared to non-polarized e-bandage (no HOCl production) and Tegaderm only controls, the polarized e-bandages reduced bacterial loads in wounds infected with MRSA plus P. aeruginosa (MRSA: vs Tegaderm only - 1.4 log10 CFU/g, p = 0.0015, vs. non-polarized - 1.1 log10 CFU/g, p = 0.026. P. aeruginosa: vs Tegaderm only - 1.6 log10 CFU/g, p = 0.0015, vs non-polarized - 1.6 log10 CFU/g, p = 0.0032), and MRSA alone (vs Tegaderm only - 1.3 log10 CFU/g, p = 0.0048, vs. non-polarized - 1.1 log10 CFU/g, p = 0.0048), without compromising wound healing or causing tissue toxicity. Addition of systemic antibiotics did not enhance the antimicrobial efficacy of e-bandages, highlighting their potential as standalone therapies. This study provides additional evidence for the HOCl-producing e-bandage as a novel antimicrobial strategy for managing wound infections, including in the context of antibiotic resistance and polymicrobial infections.

microbiology↗