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Host Response of Human Epidermis to Methicillin-Resistant Staphylococcus aureus Biofilm Infection and Synthetic Antibiofilm Peptide Treatment Wu, Bing; Blimkie, Travis M.; Haney, Evan F.; Falsafi, Reza; Akhoundsadegh, Noushin; Hancock, R. E. W. (Robert E. W.)

Abstract

Bacterial biofilm infections associated with wounded skin are prevalent, recalcitrant, and in urgent need of treatments. Additionally, host responses in the skin to biofilm infections are not well understood. Here we employed a human organoid skin model to explore the transcriptomic changes of thermally-injured epidermis to methicillin-resistant Staphylococcus aureus (MRSA) biofilm colonization. MRSA biofilm impaired skin barrier function, enhanced extracellular matrix remodelling, elicited inflammatory responses including IL-17, IL-12 family and IL-6 family interleukin signalling, and modulated skin metabolism. Synthetic antibiofilm peptide DJK-5 effectively diminished MRSA biofilm and associated skin inflammation in wounded human ex vivo skin. In the epidermis, DJK-5 shifted the overall skin transcriptome towards homeostasis including modulating the biofilm induced inflammatory response, promoting the skin DNA repair function, and downregulating MRSA invasion of thermally damaged skin. These data clarified the underlying immunopathogenesis of biofilm infections and revealed the intrinsic promise of synthetic peptides in reducing inflammation and biofilm infections.

Item Metadata

Title
Host Response of Human Epidermis to Methicillin-Resistant Staphylococcus aureus Biofilm Infection and Synthetic Antibiofilm Peptide Treatment
Creator
Wu, Bing; Blimkie, Travis M.; Haney, Evan F.; Falsafi, Reza; Akhoundsadegh, Noushin; Hancock, R. E. W. (Robert E. W.)
Publisher
Multidisciplinary Digital Publishing Institute
Date Issued
2022-11-01
Description
Bacterial biofilm infections associated with wounded skin are prevalent, recalcitrant, and in urgent need of treatments. Additionally, host responses in the skin to biofilm infections are not well understood. Here we employed a human organoid skin model to explore the transcriptomic changes of thermally-injured epidermis to methicillin-resistant Staphylococcus aureus (MRSA) biofilm colonization. MRSA biofilm impaired skin barrier function, enhanced extracellular matrix remodelling, elicited inflammatory responses including IL-17, IL-12 family and IL-6 family interleukin signalling, and modulated skin metabolism. Synthetic antibiofilm peptide DJK-5 effectively diminished MRSA biofilm and associated skin inflammation in wounded human ex vivo skin. In the epidermis, DJK-5 shifted the overall skin transcriptome towards homeostasis including modulating the biofilm induced inflammatory response, promoting the skin DNA repair function, and downregulating MRSA invasion of thermally damaged skin. These data clarified the underlying immunopathogenesis of biofilm infections and revealed the intrinsic promise of synthetic peptides in reducing inflammation and biofilm infections.
Subject
biofilm immunopathogenesis; innate immune response; inflammation; skin barrier function; extracellular matrix remodeling; DNA repair; host defense peptide; human skin; RNA-Seq transcriptomic analysis
Genre
Article
Type
Text
Language
eng
Date Available
2025-01-24
Provider
Vancouver : University of British Columbia Library
Rights
CC BY 4.0
DOI
10.14288/1.0447831
URI
http://hdl.handle.net/2429/90196
Affiliation
Science, Faculty of; Microbiology and Immunology, Department of
Citation
Cells 11 (21): 3459 (2022)
Publisher DOI
10.3390/cells11213459
Peer Review Status
Reviewed
Scholarly Level
Faculty; Researcher
Rights URI
https://creativecommons.org/licenses/by/4.0/
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CC BY 4.0