Dual Antimicrobial and Immunomodulatory Activities of a Bioengineered Reactive Oxygen Species Releasing Gel Against Multidrug-Resistant Staphylococcus aureus
Rebecca E. Holding, Olivia K. Lee, Timothy C. Biggs, Raymond N. Allan, Ali A. Salamat, Rami J. Salib, Sylvia L. F. PenderIn this study, we evaluated the antimicrobial and immunomodulatory properties of a novel bioengineered reactive oxygen species (ROS) gel that releases sustained, low concentrations of hydrogen peroxide (H2O2) upon hydration. The efficacy of the ROS gel was assessed against a multidrug-resistant clinical isolate of Staphylococcus aureus, and its effects on host defence were evaluated using human nasal epithelial cells and mast cells. The ROS gel significantly reduced Staphylococcus aureus biofilm viability while simultaneously upregulating genes involved in innate and adaptive host defence. Sustained H2O2 release enhanced the expression of antimicrobial peptides, toll-like receptor 4, and transcription factors associated with Th17 (RORC) and Th2 (GATA3) immune responses. In addition, the ROS gel modulated the expression of matrix metalloproteinases (MMP7 and MMP9) and IL10, suggesting a role in tissue remodelling and resolution of inflammation. These findings demonstrate that the ROS gel exerts dual therapeutic effects by directly inhibiting bacterial growth while modulating host transcriptional immune-associated gene responses. Harnessing ROS-based therapies may reduce reliance on conventional antibiotics and help limit the progression of antimicrobial resistance.