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Article: Dehydrosqualene Desaturase as a Novel Target for Anti-Virulence Therapy against Staphylococcus aureus

TitleDehydrosqualene Desaturase as a Novel Target for Anti-Virulence Therapy against Staphylococcus aureus
Authors
Issue Date2017
PublisherAmerican Society for Microbiology: Open Access Journals. The Journal's web site is located at http://mbio.asm.org
Citation
mBio, 2017, v. 8 n. 5, p. e01224-17 How to Cite?
AbstractStaphylococcus aureus, especially methicillin-resistant S. aureus (MRSA), is a life-threatening pathogen in hospital- and community-acquired infections. The golden-colored carotenoid pigment of S. aureus, staphyloxanthin, contributes to the resistance to reactive oxygen species (ROS) and host neutrophil-based killing. Here, we describe a novel inhibitor (NP16) of S. aureus pigment production that reduces the survival of S. aureus under oxidative stress conditions. Carotenoid components analysis, enzyme inhibition, and crtN mutational studies indicated that the molecular target of NP16 is dehydrosqualene desaturase (CrtN). S. aureus treated with NP16 showed increased susceptibility to human neutrophil killing and to innate immune clearance in a mouse infection model. Our study validates CrtN as a novel druggable target in S. aureus and presents a potent and effective lead compound for the development of virulence factor-based therapy against S. aureus
Persistent Identifierhttp://hdl.handle.net/10722/244404
ISSN
2017 Impact Factor: 6.689
2015 SCImago Journal Rankings: 3.543
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorGao, P-
dc.contributor.authorDavies, J-
dc.contributor.authorKao, RYT-
dc.date.accessioned2017-09-18T01:51:50Z-
dc.date.available2017-09-18T01:51:50Z-
dc.date.issued2017-
dc.identifier.citationmBio, 2017, v. 8 n. 5, p. e01224-17-
dc.identifier.issn2150-7511-
dc.identifier.urihttp://hdl.handle.net/10722/244404-
dc.description.abstractStaphylococcus aureus, especially methicillin-resistant S. aureus (MRSA), is a life-threatening pathogen in hospital- and community-acquired infections. The golden-colored carotenoid pigment of S. aureus, staphyloxanthin, contributes to the resistance to reactive oxygen species (ROS) and host neutrophil-based killing. Here, we describe a novel inhibitor (NP16) of S. aureus pigment production that reduces the survival of S. aureus under oxidative stress conditions. Carotenoid components analysis, enzyme inhibition, and crtN mutational studies indicated that the molecular target of NP16 is dehydrosqualene desaturase (CrtN). S. aureus treated with NP16 showed increased susceptibility to human neutrophil killing and to innate immune clearance in a mouse infection model. Our study validates CrtN as a novel druggable target in S. aureus and presents a potent and effective lead compound for the development of virulence factor-based therapy against S. aureus-
dc.languageeng-
dc.publisherAmerican Society for Microbiology: Open Access Journals. The Journal's web site is located at http://mbio.asm.org-
dc.relation.ispartofmBio-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleDehydrosqualene Desaturase as a Novel Target for Anti-Virulence Therapy against Staphylococcus aureus-
dc.typeArticle-
dc.identifier.emailGao, P: gaopeng@hku.hk-
dc.identifier.emailKao, RYT: rytkao@hkucc.hku.hk-
dc.identifier.authorityKao, RYT=rp00481-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1128/mBio.01224-17-
dc.identifier.hkuros278389-
dc.identifier.volume8-
dc.identifier.issue5-
dc.identifier.spagee01224-
dc.identifier.epage17-
dc.identifier.isiWOS:000416271100035-
dc.publisher.placeUnited States-

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