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

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

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.728989

DOI=10.3389/fmicb.2021.728989

ISSN=1664-302X

ABSTRACT=<p>The healthy human epidermis provides physical protection and is impenetrable for pathogenic microbes. Nevertheless, commensal and pathogen bacteria such as <italic>Staphylococcus aureus</italic> are able to colonize the skin surface, which may subsequently lead to infection. To identify and characterize regulatory elements facilitating adaptation of <italic>S. aureus</italic> to the human skin environment we used <italic>ex vivo</italic> tissue explants and quantified <italic>S. aureus</italic> gene transcription during co-culture. This analysis provided evidence for a significant downregulation of the global virulence regulator <italic>agr</italic> upon initial contact with skin, regardless of the growth phase of <italic>S. aureus</italic> prior to co-culture. In contrast, the alternative sigma factor B (<italic>sig</italic>B) and the antimicrobial peptide-sensing system (<italic>gra</italic>RS) were expressed during early colonization. Consistently, <italic>sig</italic>B target genes such as the clumping factor A (<italic>clf</italic>A) and fibrinogen and fibronectin binding protein A (<italic>fnb</italic>A) 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 (<italic>sce</italic>D and <italic>atl</italic>A) 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 <italic>ex vivo</italic> skin colonization model that allows the detailed characterization of the bacterial adaptation to the skin environment.</p>