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Updated: Apr 21, 2026
Standardized In vitro Assays to Visualize and Quantify Interactions between Human Neutrophils and Staphylococcus aureus Biofilms
Published on: June 8, 2022
Synergistic tissue destruction by Staphylococcus aureus and Staphylococcus epidermidis in a 3D human skin biofilm
Rima Nuwayhid1, Nguyen Ngoc-Huyen2, Norman Lippmann3
1Department of Orthopaedic, Trauma and Plastic Surgery, University Hospital Leipzig, 04103, Leipzig, Germany.
Abstract:
Staphylococci are common skin commensals that can transition into opportunistic pathogens, particularly in biofilm-associated and polymicrobial infections. However, how interspecies interactions modulate virulence remains poorly understood, partly due to a lack of human-relevant models. We adapted a human cell-based three-dimensional skin equivalent (3DSE) into a biofilm infection model using monospecies biofilms of Staphylococcus aureus or Staphylococcus epidermidis, and a dualspecies co-culture. Biofilm architecture and spatial distribution were analysed by histology and fluorescence in situ hybridisation, while bacterial dominance was assessed by colony-forming unit counts. Host responses were evaluated using a composite biofilm destruction score, lactate dehydrogenase release, apoptosis and tight junction integrity, and cytokine profiling. The 3DSE supported robust, species-specific biofilm formation. Notably, despite reduced biofilm mass, dualspecies biofilms caused the most severe tissue damage, cytotoxicity and epithelial disruption. Although S. aureus dominated in co-culture, pathogenicity was not dependent on bacterial load. These findings demonstrate synergistic host modulation in polymicrobial staphylococcal biofilms and establish the 3DSE as a physiologically relevant platform for studying skin biofilm infections.
Insights
Polymicrobial biofilms of Staphylococcus aureus and Staphylococcus epidermidis cause severe skin damage, even with less biomass. A 3D skin model reveals synergistic virulence in these common skin bacteria.
Area of Science:
- Microbiology
- Dermatology
- Infectious Diseases
Background:
- Staphylococci are common skin bacteria that can cause opportunistic infections, especially in biofilms.
- Understanding how different bacterial species interact to cause disease is crucial but limited by a lack of human-relevant models.
Purpose of the Study:
- To adapt a human three-dimensional skin equivalent (3DSE) into a model for studying staphylococcal biofilm infections.
- To investigate the impact of monospecies and dual-species staphylococcal biofilms on host tissue.
Main Methods:
- Developed a 3DSE biofilm infection model using Staphylococcus aureus and Staphylococcus epidermidis.
- Analyzed biofilm architecture, bacterial distribution, and host responses including tissue damage, cytotoxicity, and cytokine profiles.
Main Results:
- The 3DSE supported robust, species-specific biofilm formation.
- Dual-species biofilms, despite reduced mass, induced significantly more severe tissue damage, cytotoxicity, and epithelial disruption compared to monospecies biofilms.
- Staphylococcus aureus dominated dual-species biofilms, but pathogenicity was not directly correlated with bacterial load.
Conclusions:
- Polymicrobial staphylococcal biofilms exhibit synergistic virulence, leading to enhanced host tissue damage.
- The 3DSE is a valuable and physiologically relevant platform for studying complex skin biofilm infections.
Related Concept Videos
01:29Staphylococcal Skin Infections
01:27The Skin Microbiota
01:29Biofilms