Selective Depletion of Staphylococcus aureus Restores the Skin Microbiome and Accelerates Tissue Repair after Injury.

Autor:	Wilkinson HN; Biomedical Institute for Multimorbidity, Centre for Biomedicine, Hull York Medical School, The University of Hull, Hull, United Kingdom; Skin Research Centre, Hull York Medical School, The University of York, Heslington, United Kingdom. Electronic address: h.n.wilkinson@hull.ac.uk., Stafford AR; Biomedical Institute for Multimorbidity, Centre for Biomedicine, Hull York Medical School, The University of Hull, Hull, United Kingdom., Rudden M; Biomedical Institute for Multimorbidity, Centre for Biomedicine, Hull York Medical School, The University of Hull, Hull, United Kingdom; Skin Research Centre, Hull York Medical School, The University of York, Heslington, United Kingdom., Rocha NDC; Biomedical Institute for Multimorbidity, Centre for Biomedicine, Hull York Medical School, The University of Hull, Hull, United Kingdom., Kidd AS; Biomedical Institute for Multimorbidity, Centre for Biomedicine, Hull York Medical School, The University of Hull, Hull, United Kingdom., Iveson S; Biomedical Institute for Multimorbidity, Centre for Biomedicine, Hull York Medical School, The University of Hull, Hull, United Kingdom., Bell AL; Cica Biomedical, Knaresborough, United Kingdom., Hart J; Cica Biomedical, Knaresborough, United Kingdom., Duarte A; Micreos Pharma B.V., Bilthoven, The Netherlands., Frieling J; Micreos Pharma B.V., Bilthoven, The Netherlands., Janssen F; Micreos Pharma B.V., Bilthoven, The Netherlands., Röhrig C; Micreos Pharma B.V., Bilthoven, The Netherlands., de Rooij B; Micreos Pharma B.V., Bilthoven, The Netherlands., Ekhart PF; InnoPact B.V., Ouderkerk aan de Amstel, The Netherlands., Hardman MJ; Biomedical Institute for Multimorbidity, Centre for Biomedicine, Hull York Medical School, The University of Hull, Hull, United Kingdom; Skin Research Centre, Hull York Medical School, The University of York, Heslington, United Kingdom.
Jazyk:	angličtina
Zdroj:	The Journal of investigative dermatology [J Invest Dermatol] 2024 Aug; Vol. 144 (8), pp. 1865-1876.e3. Date of Electronic Publication: 2024 Feb 01.
DOI:	10.1016/j.jid.2024.01.018
Abstrakt:	Our skin is home to a diverse community of commensal microorganisms integral to cutaneous function. However, microbial dysbiosis and barrier perturbation increase the risk of local and systemic infection. Staphylococcus aureus is a particularly problematic bacterial pathogen, with high levels of antimicrobial resistance and direct association with poor healing outcome. Innovative approaches are needed to selectively kill skin pathogens, such as S aureus, without harming the resident microbiota. In this study, we provide important data on the selectivity and efficacy of an S aureus-targeted endolysin (XZ.700) within the complex living skin/wound microbiome. Initial cross-species comparison using Nanopore long-read sequencing identified the translational potential of porcine rather than murine skin for human-relevant microbiome studies. We therefore performed an interventional study in pigs to assess the impact of endolysin administration on the microbiome. XZ.700 selectively inhibited endogenous porcine S aureus in vivo, restoring microbial diversity and promoting multiple aspects of wound repair. Subsequent mechanistic studies confirmed the importance of this microbiome modulation for effective healing in human skin. Taken together, these findings strongly support further development of S aureus-targeted endolysins for future clinical management of skin and wound infections. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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