Electrical stimulation disrupts biofilms in a human wound model and reveals the potential for monitoring treatment response with volatile biomarkers

Abstract

Management of biofilm infections relies on time‐consuming laboratory techniques and monitoring treatment by subjective clinical evaluations. Due to these limitations, there is a need to explore alternative strategies. The aims of this study were to assess the feasibility of using volatile organic compound (VOC) biomarkers to monitor treatment response and measure anti‐biofilm efficacy of electrical stimulation (ES) in vitro and in human cutaneous wound biofilm models. Staphylococcus aureus (MSSA) and Pseudomonas aeruginosa (PA) biofilms were exposed to ES, ciprofloxacin, or both, with efficacy assessed and quantified by fluorescence staining, enumeration, metabolic assays, and biomass quantification; VOCs were measured by gas chromatography–mass spectrometry. In vitro MSSA and PA and ex vivo PA biofilms exposed to ES showed significantly reduced bacterial viability, metabolic activity, and biomass compared to controls (p < 0.05). There was significant variation in the relative abundance of VOCs in in vitro MSSA and PA and in ex vivo PA biofilms exposed to ES and antibiotic (p < 0.05). 2‐methyl‐1‐propanol was associated with MSSA viability (R = 0.93, p < 0.05), biomass (R = 0.97, p < 0.05), and metabolic activity (R = 0.93, p < 0.05) and 3‐methyl‐1‐butanol was associated with PA biomass (R = 0.93, p < 0.05). We showed that ES and VOC biomarkers are possible options for alternative nonpharmacological antimicrobial management of biofilms and noninvasive monitoring of wound infection treatment responses, respectively.

Volatilomes of Bacterial Infections in Humans

“…Wounds are a major burden on healthcare systems because their treatment is often complicated with chronic infections and potentially the development of biofilms, which makes their eradication arduous. The volatilomes of S. aureus and P. aeruginosa biofilms have been recently studied for their potential in monitoring biofilm development and response to various treatments (Ashrafi et al, 2018(Ashrafi et al, , 2019.…”

Multi-strain volatile profiling of pathogenic and commensal cutaneous bacteria

“…The results from studies are also influenced by the sampling techniques employed. Frequently used sampling techniques coupled with GC-MS include SPME 26,27 , thermal desorption tubes 21 , direct syringes 28,29 . Direct detection methods such as SIFT-MS 26 , SESI-MS 30 and PTR-MS 31 have been previously employed for real-time analysis of VOCs, however, the resulting VOC profiles obtained from these methods typically contain low numbers of compounds.…”

An Investigation of Stability and Species and Strain-Level Specificity in Bacterial Volatilomes

“…Another less studied factor in the overall variation seen across the volatilomes of microbial species is the occurrence of strain-level specificity in volatilomic emission within a given species ( Schulz et al, 2020 ; Weisskopf et al, 2021 ). In addition to this, the variation in sampling [SPME ( Timm et al, 2018 ; Fitzgerald et al, 2020 ), thermal desorption tubes ( Filipiak et al, 2012a , b ), direct syringe ( Ashrafi et al, 2018a , b )] and analytical techniques [gas chromatography–mass spectrometry (GC-MS) ( Filipiak et al, 2012b ; Timm et al, 2018 ; Fitzgerald et al, 2020 ), selected ion-flow-tube (SIFT) MS ( Shestivska et al, 2015 ), proton transfer reaction (PTR) MS ( Bunge et al, 2008 )] employed across the field also have a direct influence on the VOC profiles reported in the literature. Consequently, cross-study validation of reported microbial VOC profiles remains a major challenge in the field.…”