Host Response of Human Epidermis to Methicillin-Resistant Staphylococcus aureus Biofilm Infection and Synthetic Antibiofilm Peptide Treatment

Abstract

Bacterial biofilm infections associated with wounded skin are prevalent, recalcitrant, and in urgent need of treatments. Additionally, host responses in the skin to biofilm infections are not well understood. Here we employed a human organoid skin model to explore the transcriptomic changes of thermally-injured epidermis to methicillin-resistant Staphylococcus aureus (MRSA) biofilm colonization. MRSA biofilm impaired skin barrier function, enhanced extracellular matrix remodelling, elicited inflammatory responses including IL-17, IL-12 family and IL-6 family interleukin signalling, and modulated skin metabolism. Synthetic antibiofilm peptide DJK-5 effectively diminished MRSA biofilm and associated skin inflammation in wounded human ex vivo skin. In the epidermis, DJK-5 shifted the overall skin transcriptome towards homeostasis including modulating the biofilm induced inflammatory response, promoting the skin DNA repair function, and downregulating MRSA invasion of thermally damaged skin. These data clarified the underlying immunopathogenesis of biofilm infections and revealed the intrinsic promise of synthetic peptides in reducing inflammation and biofilm infections.

The Synergistic Antimicrobial Effect and Mechanism of Nisin and Oxacillin against Methicillin-Resistant Staphylococcus aureus

“…Because the concentration of antibiotics decreases significantly when penetrating into the biofilm, bacteria are more likely to develop drug resistance when stimulated by low concentrations of antibiotics [ 18 ]. In addition, the metabolism of MRSA in biofilms is also reduced, hence the sensitivity to antibiotics is significantly reduced, which is the main reason for the difficulty in completely removing the foci of chronic infection [ 19 ]. Here, we demonstrated that, single OX treatment could inhibit the biofilm formation of MRSA Yn2020043 and Yn2020070, while significantly stimulated on MRSA Yn2020051 and MSSA ATCC25923, suggests that the responses of different S. aureus strains to OX may be quite different.…”

Biology and Regulation of Staphylococcal Biofilm

“…Dozens of recent papers described different attempts to reduce biofilm formation or to destroy an already-formed biofilm in order to avoid the removal or replacement of an implanted material. Enzymes, antimicrobial peptides, bacteriophages, and natural compounds from vegetal origins have been used, mainly in vitro, with variable results [ 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 ]. Interesting observations were reported by Caballero Gomez in the field of meat-chain production using natural compounds extracted from essential oils alone or in combination with EDTA [ 133 ].…”

“…Other natural molecules have been identified from human milk, such as oligosaccharides, that allow for an appreciable decrease in S. aureus biofilm formation [ 136 ]. Other groups reported the efficacy of different synthetic molecules of an organic [ 134 , 139 ] or peptidic [ 135 ] nature on biofilm formation with clear success. Impressive results were obtained using a non-toxic acyclic amine derivative that yielded an extensive reduction of a biofilm and bacterial count in a model of urinary catheter infection [ 139 ].…”

MXene/TPU Hybrid Fabrics Enable Smart Wound Management and Thermoresponsive Drug Delivery

“…The skin, being the largest organ of the human body, plays a crucial role in defending against external pathogens and toxins while maintaining optimal water and heat balance within the body. − Therefore, the timely repair of wounds is essential for maintaining the normal physiological levels of the human body. − The persistent inflammation triggered by bacterial infection hinders wound healing and leads to the development of chronic wounds, imposing a significant burden on global healthcare systems and economies. − Currently, the utilization of wound dressings remains the primary approach for managing wounds in clinical practice. , However, conventional wound dressings (such as gauze, , bandages, etc.) merely passively deliver medications and protect the wound.…”