Dehydrosqualene Desaturase as a Novel Target for Anti-Virulence Therapy against <italic toggle="yes">Staphylococcus aureus</italic>

ABSTRACT Staphylococcus 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 ho...

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Autores principales:	Peng Gao, Julian Davies, Richard Yi Tsun Kao
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	MRSA anti-virulence bacterial infection staphyloxanthin Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/581d788f7be34a8295d4091f0f33fffc
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spelling	oai:doaj.org-article:581d788f7be34a8295d4091f0f33fffc2021-11-15T15:51:51ZDehydrosqualene Desaturase as a Novel Target for Anti-Virulence Therapy against <italic toggle="yes">Staphylococcus aureus</italic>10.1128/mBio.01224-172150-7511https://doaj.org/article/581d788f7be34a8295d4091f0f33fffc2017-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01224-17https://doaj.org/toc/2150-7511ABSTRACT Staphylococcus 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. IMPORTANCE S. aureus staphyloxanthin contributes substantially to pathogenesis by interfering with host immune clearance mechanisms, but it has little impact on ex vivo survival of the bacterium. Agents blocking staphyloxanthin production may discourage the establishment and maintenance of bacterial infection without exerting selective pressure for antimicrobial resistance. Our newly discovered CrtN inhibitor, NP16, may offer an effective strategy for combating S. aureus infections.Peng GaoJulian DaviesRichard Yi Tsun KaoAmerican Society for MicrobiologyarticleMRSAanti-virulencebacterial infectionstaphyloxanthinMicrobiologyQR1-502ENmBio, Vol 8, Iss 5 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	MRSA anti-virulence bacterial infection staphyloxanthin Microbiology QR1-502
spellingShingle	MRSA anti-virulence bacterial infection staphyloxanthin Microbiology QR1-502 Peng Gao Julian Davies Richard Yi Tsun Kao Dehydrosqualene Desaturase as a Novel Target for Anti-Virulence Therapy against <italic toggle="yes">Staphylococcus aureus</italic>
description	ABSTRACT Staphylococcus 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. IMPORTANCE S. aureus staphyloxanthin contributes substantially to pathogenesis by interfering with host immune clearance mechanisms, but it has little impact on ex vivo survival of the bacterium. Agents blocking staphyloxanthin production may discourage the establishment and maintenance of bacterial infection without exerting selective pressure for antimicrobial resistance. Our newly discovered CrtN inhibitor, NP16, may offer an effective strategy for combating S. aureus infections.
format	article
author	Peng Gao Julian Davies Richard Yi Tsun Kao
author_facet	Peng Gao Julian Davies Richard Yi Tsun Kao
author_sort	Peng Gao
title	Dehydrosqualene Desaturase as a Novel Target for Anti-Virulence Therapy against <italic toggle="yes">Staphylococcus aureus</italic>
title_short	Dehydrosqualene Desaturase as a Novel Target for Anti-Virulence Therapy against <italic toggle="yes">Staphylococcus aureus</italic>
title_full	Dehydrosqualene Desaturase as a Novel Target for Anti-Virulence Therapy against <italic toggle="yes">Staphylococcus aureus</italic>
title_fullStr	Dehydrosqualene Desaturase as a Novel Target for Anti-Virulence Therapy against <italic toggle="yes">Staphylococcus aureus</italic>
title_full_unstemmed	Dehydrosqualene Desaturase as a Novel Target for Anti-Virulence Therapy against <italic toggle="yes">Staphylococcus aureus</italic>
title_sort	dehydrosqualene desaturase as a novel target for anti-virulence therapy against <italic toggle="yes">staphylococcus aureus</italic>
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/581d788f7be34a8295d4091f0f33fffc
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Dehydrosqualene Desaturase as a Novel Target for Anti-Virulence Therapy against <italic toggle="yes">Staphylococcus aureus</italic>

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