Propyl-5-hydroxy-3-methyl-1-phenyl-1H-pyrazole-4-carbodithioate (HMPC): a new bacteriostatic agent against methicillin—resistant Staphylococcus aureus

Abstract The emergence of Staphylococcus aureus strains resistant to ‘last resort’ antibiotics compels the development of new antimicrobials against this important human pathogen. We found that propyl 5-hydroxy-3-methyl-1-phenyl-1H-pyrazole-4-carbodithioate (HMPC) shows bacteriostatic activity again...

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Autores principales:	Tatiana Johnston, Daria Van Tyne, Roy F. Chen, Nicolas L. Fawzi, Bumsup Kwon, Michael J. Kelso, Michael S. Gilmore, Eleftherios Mylonakis
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7742937839174b2885ea370d1062d0f8
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spelling	oai:doaj.org-article:7742937839174b2885ea370d1062d0f82021-12-02T15:08:50ZPropyl-5-hydroxy-3-methyl-1-phenyl-1H-pyrazole-4-carbodithioate (HMPC): a new bacteriostatic agent against methicillin—resistant Staphylococcus aureus10.1038/s41598-018-25571-w2045-2322https://doaj.org/article/7742937839174b2885ea370d1062d0f82018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25571-whttps://doaj.org/toc/2045-2322Abstract The emergence of Staphylococcus aureus strains resistant to ‘last resort’ antibiotics compels the development of new antimicrobials against this important human pathogen. We found that propyl 5-hydroxy-3-methyl-1-phenyl-1H-pyrazole-4-carbodithioate (HMPC) shows bacteriostatic activity against S. aureus (MIC = 4 μg/ml) and rescues Caenorhabditis elegans from S. aureus infection. Whole-genome sequencing of S. aureus mutants resistant to the compound, along with screening of a S. aureus promoter-lux reporter array, were used to explore possible mechanisms of action. All mutants resistant to HMPC acquired missense mutations at distinct codon positions in the global transcriptional regulator mgrA, followed by secondary mutations in the phosphatidylglycerol lysyltransferase fmtC/mprF. The S. aureus promoter-lux array treated with HMPC displayed a luminescence profile that was unique but showed similarity to DNA-damaging agents and/or DNA replication inhibitors. Overall, HMPC is a new anti-staphylococcal compound that appears to act via an unknown mechanism linked to the global transcriptional regulator MgrA.Tatiana JohnstonDaria Van TyneRoy F. ChenNicolas L. FawziBumsup KwonMichael J. KelsoMichael S. GilmoreEleftherios MylonakisNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tatiana Johnston Daria Van Tyne Roy F. Chen Nicolas L. Fawzi Bumsup Kwon Michael J. Kelso Michael S. Gilmore Eleftherios Mylonakis Propyl-5-hydroxy-3-methyl-1-phenyl-1H-pyrazole-4-carbodithioate (HMPC): a new bacteriostatic agent against methicillin—resistant Staphylococcus aureus
description	Abstract The emergence of Staphylococcus aureus strains resistant to ‘last resort’ antibiotics compels the development of new antimicrobials against this important human pathogen. We found that propyl 5-hydroxy-3-methyl-1-phenyl-1H-pyrazole-4-carbodithioate (HMPC) shows bacteriostatic activity against S. aureus (MIC = 4 μg/ml) and rescues Caenorhabditis elegans from S. aureus infection. Whole-genome sequencing of S. aureus mutants resistant to the compound, along with screening of a S. aureus promoter-lux reporter array, were used to explore possible mechanisms of action. All mutants resistant to HMPC acquired missense mutations at distinct codon positions in the global transcriptional regulator mgrA, followed by secondary mutations in the phosphatidylglycerol lysyltransferase fmtC/mprF. The S. aureus promoter-lux array treated with HMPC displayed a luminescence profile that was unique but showed similarity to DNA-damaging agents and/or DNA replication inhibitors. Overall, HMPC is a new anti-staphylococcal compound that appears to act via an unknown mechanism linked to the global transcriptional regulator MgrA.
format	article
author	Tatiana Johnston Daria Van Tyne Roy F. Chen Nicolas L. Fawzi Bumsup Kwon Michael J. Kelso Michael S. Gilmore Eleftherios Mylonakis
author_facet	Tatiana Johnston Daria Van Tyne Roy F. Chen Nicolas L. Fawzi Bumsup Kwon Michael J. Kelso Michael S. Gilmore Eleftherios Mylonakis
author_sort	Tatiana Johnston
title	Propyl-5-hydroxy-3-methyl-1-phenyl-1H-pyrazole-4-carbodithioate (HMPC): a new bacteriostatic agent against methicillin—resistant Staphylococcus aureus
title_short	Propyl-5-hydroxy-3-methyl-1-phenyl-1H-pyrazole-4-carbodithioate (HMPC): a new bacteriostatic agent against methicillin—resistant Staphylococcus aureus
title_full	Propyl-5-hydroxy-3-methyl-1-phenyl-1H-pyrazole-4-carbodithioate (HMPC): a new bacteriostatic agent against methicillin—resistant Staphylococcus aureus
title_fullStr	Propyl-5-hydroxy-3-methyl-1-phenyl-1H-pyrazole-4-carbodithioate (HMPC): a new bacteriostatic agent against methicillin—resistant Staphylococcus aureus
title_full_unstemmed	Propyl-5-hydroxy-3-methyl-1-phenyl-1H-pyrazole-4-carbodithioate (HMPC): a new bacteriostatic agent against methicillin—resistant Staphylococcus aureus
title_sort	propyl-5-hydroxy-3-methyl-1-phenyl-1h-pyrazole-4-carbodithioate (hmpc): a new bacteriostatic agent against methicillin—resistant staphylococcus aureus
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/7742937839174b2885ea370d1062d0f8
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Propyl-5-hydroxy-3-methyl-1-phenyl-1H-pyrazole-4-carbodithioate (HMPC): a new bacteriostatic agent against methicillin—resistant Staphylococcus aureus

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