PMID- 34621255 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20211009 IS - 1664-302X (Print) IS - 1664-302X (Electronic) IS - 1664-302X (Linking) VI - 12 DP - 2021 TI - Adaptation of Staphylococcus aureus to the Human Skin Environment Identified Using an ex vivo Tissue Model. PG - 728989 LID - 10.3389/fmicb.2021.728989 [doi] LID - 728989 AB - 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. CI - Copyright (c) 2021 Burian, Plange, Schmitt, Kaschke, Marquardt, Huth, Baron, Hornef, Wolz and Yazdi. FAU - Burian, Marc AU - Burian M AD - Department of Dermatology and Allergology, RWTH University Hospital Aachen, Aachen, Germany. FAU - Plange, Johanna AU - Plange J AD - Department of Dermatology and Allergology, RWTH University Hospital Aachen, Aachen, Germany. FAU - Schmitt, Laurenz AU - Schmitt L AD - Department of Dermatology and Allergology, RWTH University Hospital Aachen, Aachen, Germany. FAU - Kaschke, Anke AU - Kaschke A AD - Department of Dermatology and Allergology, RWTH University Hospital Aachen, Aachen, Germany. FAU - Marquardt, Yvonne AU - Marquardt Y AD - Department of Dermatology and Allergology, RWTH University Hospital Aachen, Aachen, Germany. FAU - Huth, Laura AU - Huth L AD - Department of Dermatology and Allergology, RWTH University Hospital Aachen, Aachen, Germany. FAU - Baron, Jens M AU - Baron JM AD - Department of Dermatology and Allergology, RWTH University Hospital Aachen, Aachen, Germany. FAU - Hornef, Mathias W AU - Hornef MW AD - Institute of Medical Microbiology, RWTH University Hospital Aachen, Aachen, Germany. FAU - Wolz, Christiane AU - Wolz C AD - Interfaculty Institute of Microbiology and Infection Medicine, University of Tuebingen, Tuebingen, Germany. FAU - Yazdi, Amir S AU - Yazdi AS AD - Department of Dermatology and Allergology, RWTH University Hospital Aachen, Aachen, Germany. LA - eng PT - Journal Article DEP - 20210921 PL - Switzerland TA - Front Microbiol JT - Frontiers in microbiology JID - 101548977 PMC - PMC8490888 OTO - NOTNLM OT - accessory gene regulator (agr) OT - bacterial adhesion OT - colonization OT - ex vivo skin explant OT - global regulators OT - human skin (in vivo) OT - immune evasion OT - proteases COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/10/09 06:00 MHDA- 2021/10/09 06:01 PMCR- 2021/09/21 CRDT- 2021/10/08 07:07 PHST- 2021/06/22 00:00 [received] PHST- 2021/09/01 00:00 [accepted] PHST- 2021/10/08 07:07 [entrez] PHST- 2021/10/09 06:00 [pubmed] PHST- 2021/10/09 06:01 [medline] PHST- 2021/09/21 00:00 [pmc-release] AID - 10.3389/fmicb.2021.728989 [doi] PST - epublish SO - Front Microbiol. 2021 Sep 21;12:728989. doi: 10.3389/fmicb.2021.728989. eCollection 2021.