Rapid MRSA detection via tandem mass spectrometry of the intact 80 kDa PBP2a resistance protein

Abstract Treatment of antibiotic-resistant infections is dependent on the detection of specific bacterial genes or proteins in clinical assays. Identification of methicillin-resistant Staphylococcus aureus (MRSA) is often accomplished through the detection of penicillin-binding protein 2a (PBP2a). W...

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Autores principales:	Jason R. Neil, Arvind Verma, Scott R. Kronewitter, William M. McGee, Christopher Mullen, Marjaana Viirtola, Annika Kotovuori, Herdis Friedrich, Johan Finell, Joni Rannisto, John E. P. Syka, James L. Stephenson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0dfbf32c8a3946799273c05df9f0788a
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spelling	oai:doaj.org-article:0dfbf32c8a3946799273c05df9f0788a2021-12-02T18:50:48ZRapid MRSA detection via tandem mass spectrometry of the intact 80 kDa PBP2a resistance protein10.1038/s41598-021-97844-w2045-2322https://doaj.org/article/0dfbf32c8a3946799273c05df9f0788a2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97844-whttps://doaj.org/toc/2045-2322Abstract Treatment of antibiotic-resistant infections is dependent on the detection of specific bacterial genes or proteins in clinical assays. Identification of methicillin-resistant Staphylococcus aureus (MRSA) is often accomplished through the detection of penicillin-binding protein 2a (PBP2a). With greater dependence on mass spectrometry (MS)-based bacterial identification, complementary efforts to detect resistance have been hindered by the complexity of those proteins responsible. Initial characterization of PBP2a indicates the presence of glycan modifications. To simplify detection, we demonstrate a proof-of-concept tandem MS approach involving the generation of N-terminal PBP2a peptide-like fragments and detection of unique product ions during top-down proteomic sample analyses. This approach was implemented for two PBP2a variants, PBP2amecA and PBP2amecC, and was accurate across a representative panel of MRSA strains with different genetic backgrounds. Additionally, PBP2amecA was successfully detected from clinical isolates using a five-minute liquid chromatographic separation and implementation of this MS detection strategy. Our results highlight the capability of direct MS-based resistance marker detection and potential advantages for implementing these approaches in clinical diagnostics.Jason R. NeilArvind VermaScott R. KronewitterWilliam M. McGeeChristopher MullenMarjaana ViirtolaAnnika KotovuoriHerdis FriedrichJohan FinellJoni RannistoJohn E. P. SykaJames L. StephensonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jason R. Neil Arvind Verma Scott R. Kronewitter William M. McGee Christopher Mullen Marjaana Viirtola Annika Kotovuori Herdis Friedrich Johan Finell Joni Rannisto John E. P. Syka James L. Stephenson Rapid MRSA detection via tandem mass spectrometry of the intact 80 kDa PBP2a resistance protein
description	Abstract Treatment of antibiotic-resistant infections is dependent on the detection of specific bacterial genes or proteins in clinical assays. Identification of methicillin-resistant Staphylococcus aureus (MRSA) is often accomplished through the detection of penicillin-binding protein 2a (PBP2a). With greater dependence on mass spectrometry (MS)-based bacterial identification, complementary efforts to detect resistance have been hindered by the complexity of those proteins responsible. Initial characterization of PBP2a indicates the presence of glycan modifications. To simplify detection, we demonstrate a proof-of-concept tandem MS approach involving the generation of N-terminal PBP2a peptide-like fragments and detection of unique product ions during top-down proteomic sample analyses. This approach was implemented for two PBP2a variants, PBP2amecA and PBP2amecC, and was accurate across a representative panel of MRSA strains with different genetic backgrounds. Additionally, PBP2amecA was successfully detected from clinical isolates using a five-minute liquid chromatographic separation and implementation of this MS detection strategy. Our results highlight the capability of direct MS-based resistance marker detection and potential advantages for implementing these approaches in clinical diagnostics.
format	article
author	Jason R. Neil Arvind Verma Scott R. Kronewitter William M. McGee Christopher Mullen Marjaana Viirtola Annika Kotovuori Herdis Friedrich Johan Finell Joni Rannisto John E. P. Syka James L. Stephenson
author_facet	Jason R. Neil Arvind Verma Scott R. Kronewitter William M. McGee Christopher Mullen Marjaana Viirtola Annika Kotovuori Herdis Friedrich Johan Finell Joni Rannisto John E. P. Syka James L. Stephenson
author_sort	Jason R. Neil
title	Rapid MRSA detection via tandem mass spectrometry of the intact 80 kDa PBP2a resistance protein
title_short	Rapid MRSA detection via tandem mass spectrometry of the intact 80 kDa PBP2a resistance protein
title_full	Rapid MRSA detection via tandem mass spectrometry of the intact 80 kDa PBP2a resistance protein
title_fullStr	Rapid MRSA detection via tandem mass spectrometry of the intact 80 kDa PBP2a resistance protein
title_full_unstemmed	Rapid MRSA detection via tandem mass spectrometry of the intact 80 kDa PBP2a resistance protein
title_sort	rapid mrsa detection via tandem mass spectrometry of the intact 80 kda pbp2a resistance protein
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0dfbf32c8a3946799273c05df9f0788a
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Rapid MRSA detection via tandem mass spectrometry of the intact 80 kDa PBP2a resistance protein

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