Human organoid biofilm model for assessing antibiofilm activity of novel agents

Abstract Bacterial biofilms cause 65% of all human infections and are highly resistant to antibiotic therapy but lack specific treatments. To provide a human organoid model for studying host-microbe interplay and enabling screening for novel antibiofilm agents, a human epidermis organoid model with...

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Autores principales:	Bing (Catherine) Wu, Evan F. Haney, Noushin Akhoundsadegh, Daniel Pletzer, Michael J. Trimble, Alwin E. Adriaans, Peter H. Nibbering, Robert E. W. Hancock
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Microbial ecology QR100-130
Acceso en línea:	https://doaj.org/article/6edc97ff207d4c43ab33703f19b764a3
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

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spelling	oai:doaj.org-article:6edc97ff207d4c43ab33703f19b764a32021-12-02T14:16:27ZHuman organoid biofilm model for assessing antibiofilm activity of novel agents10.1038/s41522-020-00182-42055-5008https://doaj.org/article/6edc97ff207d4c43ab33703f19b764a32021-01-01T00:00:00Zhttps://doi.org/10.1038/s41522-020-00182-4https://doaj.org/toc/2055-5008Abstract Bacterial biofilms cause 65% of all human infections and are highly resistant to antibiotic therapy but lack specific treatments. To provide a human organoid model for studying host-microbe interplay and enabling screening for novel antibiofilm agents, a human epidermis organoid model with robust methicillin-resistant Staphylococcus aureus (MRSA) USA300 and Pseudomonas aeruginosa PAO1 biofilm was developed. Treatment of 1-day and 3-day MRSA and PAO1 biofilms with antibiofilm peptide DJK-5 significantly and substantially reduced the bacterial burden. This model enabled the screening of synthetic host defense peptides, revealing their superior antibiofilm activity against MRSA compared to the antibiotic mupirocin. The model was extended to evaluate thermally wounded skin infected with MRSA biofilms resulting in increased bacterial load, cytotoxicity, and pro-inflammatory cytokine levels that were all reduced upon treatment with DJK-5. Combination treatment of DJK-5 with an anti-inflammatory peptide, 1002, further reduced cytotoxicity and skin inflammation.Bing (Catherine) WuEvan F. HaneyNoushin AkhoundsadeghDaniel PletzerMichael J. TrimbleAlwin E. AdriaansPeter H. NibberingRobert E. W. HancockNature PortfolioarticleMicrobial ecologyQR100-130ENnpj Biofilms and Microbiomes, Vol 7, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbial ecology QR100-130
spellingShingle	Microbial ecology QR100-130 Bing (Catherine) Wu Evan F. Haney Noushin Akhoundsadegh Daniel Pletzer Michael J. Trimble Alwin E. Adriaans Peter H. Nibbering Robert E. W. Hancock Human organoid biofilm model for assessing antibiofilm activity of novel agents
description	Abstract Bacterial biofilms cause 65% of all human infections and are highly resistant to antibiotic therapy but lack specific treatments. To provide a human organoid model for studying host-microbe interplay and enabling screening for novel antibiofilm agents, a human epidermis organoid model with robust methicillin-resistant Staphylococcus aureus (MRSA) USA300 and Pseudomonas aeruginosa PAO1 biofilm was developed. Treatment of 1-day and 3-day MRSA and PAO1 biofilms with antibiofilm peptide DJK-5 significantly and substantially reduced the bacterial burden. This model enabled the screening of synthetic host defense peptides, revealing their superior antibiofilm activity against MRSA compared to the antibiotic mupirocin. The model was extended to evaluate thermally wounded skin infected with MRSA biofilms resulting in increased bacterial load, cytotoxicity, and pro-inflammatory cytokine levels that were all reduced upon treatment with DJK-5. Combination treatment of DJK-5 with an anti-inflammatory peptide, 1002, further reduced cytotoxicity and skin inflammation.
format	article
author	Bing (Catherine) Wu Evan F. Haney Noushin Akhoundsadegh Daniel Pletzer Michael J. Trimble Alwin E. Adriaans Peter H. Nibbering Robert E. W. Hancock
author_facet	Bing (Catherine) Wu Evan F. Haney Noushin Akhoundsadegh Daniel Pletzer Michael J. Trimble Alwin E. Adriaans Peter H. Nibbering Robert E. W. Hancock
author_sort	Bing (Catherine) Wu
title	Human organoid biofilm model for assessing antibiofilm activity of novel agents
title_short	Human organoid biofilm model for assessing antibiofilm activity of novel agents
title_full	Human organoid biofilm model for assessing antibiofilm activity of novel agents
title_fullStr	Human organoid biofilm model for assessing antibiofilm activity of novel agents
title_full_unstemmed	Human organoid biofilm model for assessing antibiofilm activity of novel agents
title_sort	human organoid biofilm model for assessing antibiofilm activity of novel agents
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6edc97ff207d4c43ab33703f19b764a3
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Human organoid biofilm model for assessing antibiofilm activity of novel agents

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