Adaptation of Staphylococcus aureus to the Human Skin Environment Identified Using an ex vivo Tissue Model.

Marc Burian,Yvonne Marquardt,Amir S Yazdi,Johanna Plange,Laurenz Schmitt,Laura Huth,Mathias W Hornef,Anke Kaschke,Jens M Baron,Christiane Wolz

doi:10.3389/fmicb.2021.728989

Abstract

The healthy human epidermis provides physical protection and is impenetrable for pathogenic microbes. Nevertheless, commensal and pathogen bacteria such as Staphylococcus aureus are able to colonize the skin surface, which may subsequently lead to infection. To identify and characterize regulatory elements facilitating adaptation of S. aureus to the human skin environment we used ex vivo tissue explants and quantified S. aureus gene transcription during co-culture. This analysis provided evidence for a significant downregulation of the global virulence regulator agr upon initial contact with skin, regardless of the growth phase of S. aureus prior to co-culture. In contrast, the alternative sigma factor B (sigB) and the antimicrobial peptide-sensing system (graRS) were expressed during early colonization. Consistently, sigB target genes such as the clumping factor A (clfA) and fibrinogen and fibronectin binding protein A (fnbA) were strongly upregulated upon skin contact. At later timepoints of the adhesion process, wall teichoic acid (WTA) synthesis was induced. Besides the expression of adhesive molecules, transcription of molecules involved in immune evasion were increased during late colonization (staphylococcal complement inhibitor and staphylokinase). Similar to nasal colonization, enzymes involved in cell wall metabolism (sceD and atlA) were highly transcribed. Finally, we detected a strong expression of proteases from all three catalytic classes during the entire colonization process. Taken together, we here present an ex vivo skin colonization model that allows the detailed characterization of the bacterial adaptation to the skin environment.

Highlights

Healthy skin protects from microbial colonization and infection through a variety of mechanisms such as a competitive microbiota and a large number of antimicrobial and immunological effector molecules including lipids, salts, enzymes, and an acidic surface pH (Chen et al, 2018)
We hypothesize that gene expression might differ significantly once S. aureus leaves its habitat in the nose and adapts to the skin environment and that such regulatory switches contribute to successful colonization
We confirmed stable colonization of the skin samples with S. aureus by demonstrating persistent expression levels of the house keeping gene gyrB (Figure 1C). gyrB transcripts were stable over time, both from skin samples that were colonized with exponentially grown bacteria as well as from skin samples colonized with post exponentially grown bacteria

Summary

INTRODUCTION

Healthy skin protects from microbial colonization and infection through a variety of mechanisms such as a competitive microbiota and a large number of antimicrobial and immunological effector molecules including lipids, salts, enzymes, and an acidic surface pH (Chen et al, 2018). The colonization of healthy skin led to a uniform response of the pathogen independently of the human host and a similar gene expression pattern was observed when S. aureus from exponential or post exponential growth phase were inoculated. In this model which is largely deprived of immune cells, the effects of S. aureus adaptation by direct contact to the human skin can be determined, independently of infiltrating immune cells

MATERIALS AND METHODS

Ethics Statement

RESULTS

DISCUSSION

CONCLUSION AND OUTLOOK