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Inflammatory and Antimicrobial Responses to Methicillin-Resistant Staphylococcus aureus in an In Vitro Wound Infection Model

Treatment of patients with burn wound infections may become complicated by the presence of antibiotic resistant bacteria and biofilms. Herein, we demonstrate an in vitro thermal wound infection model using human skin equivalents (HSE) and biofilm-forming methicillin-resistant Staphylococcus aureus (...

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Autores principales: Haisma, Elisabeth M., Rietveld, Marion H., de Breij, Anna, van Dissel, Jaap T., El Ghalbzouri, Abdoelwaheb, Nibbering, Peter H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858326/
https://www.ncbi.nlm.nih.gov/pubmed/24340061
http://dx.doi.org/10.1371/journal.pone.0082800
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author Haisma, Elisabeth M.
Rietveld, Marion H.
de Breij, Anna
van Dissel, Jaap T.
El Ghalbzouri, Abdoelwaheb
Nibbering, Peter H.
author_facet Haisma, Elisabeth M.
Rietveld, Marion H.
de Breij, Anna
van Dissel, Jaap T.
El Ghalbzouri, Abdoelwaheb
Nibbering, Peter H.
author_sort Haisma, Elisabeth M.
collection PubMed
description Treatment of patients with burn wound infections may become complicated by the presence of antibiotic resistant bacteria and biofilms. Herein, we demonstrate an in vitro thermal wound infection model using human skin equivalents (HSE) and biofilm-forming methicillin-resistant Staphylococcus aureus (MRSA) for the testing of agents to combat such infections. Application of a liquid nitrogen-cooled metal device on HSE produced reproducible wounds characterized by keratinocyte death, detachment of the epidermal layer from the dermis, and re-epithelialization. Thermal wounding was accompanied by up-regulation of markers for keratinocyte activation, inflammation, and antimicrobial responses. Exposure of thermal wounded HSEs to MRSA resulted in significant numbers of adherent MRSA/HSE after 1 hour, and multiplication of these bacteria over 24-48 hours. Exposure to MRSA enhanced expression of inflammatory mediators such as TLR2 (but not TLR3), IL-6 and IL-8, and antimicrobial proteins human β-defensin-2, -3 and RNAse7 by thermal wounded as compared to control HSEs. Moreover, locally applied mupirocin effectively reduced MRSA counts on (thermal wounded) HSEs by more than 99.9% within 24 hours. Together, these data indicate that this thermal wound infection model is a promising tool to study the initial phase of wound colonization and infection, and to assess local effects of candidate antimicrobial agents.
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spelling pubmed-38583262013-12-11 Inflammatory and Antimicrobial Responses to Methicillin-Resistant Staphylococcus aureus in an In Vitro Wound Infection Model Haisma, Elisabeth M. Rietveld, Marion H. de Breij, Anna van Dissel, Jaap T. El Ghalbzouri, Abdoelwaheb Nibbering, Peter H. PLoS One Research Article Treatment of patients with burn wound infections may become complicated by the presence of antibiotic resistant bacteria and biofilms. Herein, we demonstrate an in vitro thermal wound infection model using human skin equivalents (HSE) and biofilm-forming methicillin-resistant Staphylococcus aureus (MRSA) for the testing of agents to combat such infections. Application of a liquid nitrogen-cooled metal device on HSE produced reproducible wounds characterized by keratinocyte death, detachment of the epidermal layer from the dermis, and re-epithelialization. Thermal wounding was accompanied by up-regulation of markers for keratinocyte activation, inflammation, and antimicrobial responses. Exposure of thermal wounded HSEs to MRSA resulted in significant numbers of adherent MRSA/HSE after 1 hour, and multiplication of these bacteria over 24-48 hours. Exposure to MRSA enhanced expression of inflammatory mediators such as TLR2 (but not TLR3), IL-6 and IL-8, and antimicrobial proteins human β-defensin-2, -3 and RNAse7 by thermal wounded as compared to control HSEs. Moreover, locally applied mupirocin effectively reduced MRSA counts on (thermal wounded) HSEs by more than 99.9% within 24 hours. Together, these data indicate that this thermal wound infection model is a promising tool to study the initial phase of wound colonization and infection, and to assess local effects of candidate antimicrobial agents. Public Library of Science 2013-12-10 /pmc/articles/PMC3858326/ /pubmed/24340061 http://dx.doi.org/10.1371/journal.pone.0082800 Text en © 2013 Haisma et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Haisma, Elisabeth M.
Rietveld, Marion H.
de Breij, Anna
van Dissel, Jaap T.
El Ghalbzouri, Abdoelwaheb
Nibbering, Peter H.
Inflammatory and Antimicrobial Responses to Methicillin-Resistant Staphylococcus aureus in an In Vitro Wound Infection Model
title Inflammatory and Antimicrobial Responses to Methicillin-Resistant Staphylococcus aureus in an In Vitro Wound Infection Model
title_full Inflammatory and Antimicrobial Responses to Methicillin-Resistant Staphylococcus aureus in an In Vitro Wound Infection Model
title_fullStr Inflammatory and Antimicrobial Responses to Methicillin-Resistant Staphylococcus aureus in an In Vitro Wound Infection Model
title_full_unstemmed Inflammatory and Antimicrobial Responses to Methicillin-Resistant Staphylococcus aureus in an In Vitro Wound Infection Model
title_short Inflammatory and Antimicrobial Responses to Methicillin-Resistant Staphylococcus aureus in an In Vitro Wound Infection Model
title_sort inflammatory and antimicrobial responses to methicillin-resistant staphylococcus aureus in an in vitro wound infection model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858326/
https://www.ncbi.nlm.nih.gov/pubmed/24340061
http://dx.doi.org/10.1371/journal.pone.0082800
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