Early-Stage <italic toggle="yes">Staphylococcus aureus</italic> Bloodstream Infection Causes Changes in the Concentrations of Lipoproteins and Acute-Phase Proteins and Is Associated with Low Antibody Titers against Bacterial Virulence Factors

ABSTRACT Systemic and quantitative investigations of human plasma proteins (proteomics) and Staphylococcus aureus-specific antibodies (immunoproteomics) provide complementary information and hold promise for the discovery of biomarkers in Staphylococcus aureus bloodstream infection (SABSI). Usually,...

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Autores principales:	Stephan Michalik, Nandakumar Sundaramoorthy, Annette Murr, Maren Depke, Uwe Völker, Barbara M. Bröker, Hege Vangstein Aamot, Frank Schmidt
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	DIA mass spectrometry Staphylococcus aureus biomarker bloodstream infections immunoproteomics proteomics Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/3572e81656174a26a0de9cae2d5fb482
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spelling	oai:doaj.org-article:3572e81656174a26a0de9cae2d5fb4822021-12-02T19:47:34ZEarly-Stage <italic toggle="yes">Staphylococcus aureus</italic> Bloodstream Infection Causes Changes in the Concentrations of Lipoproteins and Acute-Phase Proteins and Is Associated with Low Antibody Titers against Bacterial Virulence Factors10.1128/mSystems.00632-192379-5077https://doaj.org/article/3572e81656174a26a0de9cae2d5fb4822020-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00632-19https://doaj.org/toc/2379-5077ABSTRACT Systemic and quantitative investigations of human plasma proteins (proteomics) and Staphylococcus aureus-specific antibodies (immunoproteomics) provide complementary information and hold promise for the discovery of biomarkers in Staphylococcus aureus bloodstream infection (SABSI). Usually, data-dependent acquisition (DDA) is used for proteome analysis of serum or plasma, but data-independent acquisition (DIA) is more comprehensive and reproducible. In this prospective cohort study, we aimed to identify biomarkers associated with the early stages of SABSI using a serum DIA proteomic and immunoproteomic approach. Sera from 49 SABSI patients and 43 noninfected controls were analyzed. In total, 608 human serum proteins were identified with DIA. A total of 386 proteins could be quantified, of which 9 proteins, mainly belonging to acute-phase proteins, were significantly increased, while 7 high-density lipoproteins were lower in SABSI. In SABSI, total anti-S. aureus serum IgG was reduced compared with controls as shown by immunoproteomic quantification of IgG binding to 143 S. aureus antigens. IgG binding to 48 of these anti-S. aureus proteins was significantly lower in SABSI, while anti-Ecb IgG was the only one increased in SABSI. Serum IgG binding to autoinducing peptide MsrB, FadB, EsxA, Pbp2, FadB, SspB, or SodA was very low in SABSI. This marker panel discriminated early SABSI from controls with 95% sensitivity and 100% specificity according to random forest prediction. This holds promise for patient stratification according to their risk of S. aureus infection, underlines the protective function of the adaptive immune system, and encourages further efforts in the development of a vaccine against S. aureus. IMPORTANCE S. aureus sepsis has a high complication and mortality rate. Given the limited therapeutic possibilities, effective prevention strategies, e.g., a vaccine, or the early identification of high-risk patients would be important but are not available. Our study showed an acute-phase response in patients with S. aureus bloodstream infection and evidence that lipoproteins are downregulated in plasma. Using immunoproteomics, stratification of patients appears to be achievable, since at the early stages of systemic S. aureus infection patients had low preexisting anti-S. aureus antibody levels. This strengthens the notion that a robust immune memory for S. aureus protects against infections with the pathogen.Stephan MichalikNandakumar SundaramoorthyAnnette MurrMaren DepkeUwe VölkerBarbara M. BrökerHege Vangstein AamotFrank SchmidtAmerican Society for MicrobiologyarticleDIA mass spectrometryStaphylococcus aureusbiomarkerbloodstream infectionsimmunoproteomicsproteomicsMicrobiologyQR1-502ENmSystems, Vol 5, Iss 1 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	DIA mass spectrometry Staphylococcus aureus biomarker bloodstream infections immunoproteomics proteomics Microbiology QR1-502
spellingShingle	DIA mass spectrometry Staphylococcus aureus biomarker bloodstream infections immunoproteomics proteomics Microbiology QR1-502 Stephan Michalik Nandakumar Sundaramoorthy Annette Murr Maren Depke Uwe Völker Barbara M. Bröker Hege Vangstein Aamot Frank Schmidt Early-Stage <italic toggle="yes">Staphylococcus aureus</italic> Bloodstream Infection Causes Changes in the Concentrations of Lipoproteins and Acute-Phase Proteins and Is Associated with Low Antibody Titers against Bacterial Virulence Factors
description	ABSTRACT Systemic and quantitative investigations of human plasma proteins (proteomics) and Staphylococcus aureus-specific antibodies (immunoproteomics) provide complementary information and hold promise for the discovery of biomarkers in Staphylococcus aureus bloodstream infection (SABSI). Usually, data-dependent acquisition (DDA) is used for proteome analysis of serum or plasma, but data-independent acquisition (DIA) is more comprehensive and reproducible. In this prospective cohort study, we aimed to identify biomarkers associated with the early stages of SABSI using a serum DIA proteomic and immunoproteomic approach. Sera from 49 SABSI patients and 43 noninfected controls were analyzed. In total, 608 human serum proteins were identified with DIA. A total of 386 proteins could be quantified, of which 9 proteins, mainly belonging to acute-phase proteins, were significantly increased, while 7 high-density lipoproteins were lower in SABSI. In SABSI, total anti-S. aureus serum IgG was reduced compared with controls as shown by immunoproteomic quantification of IgG binding to 143 S. aureus antigens. IgG binding to 48 of these anti-S. aureus proteins was significantly lower in SABSI, while anti-Ecb IgG was the only one increased in SABSI. Serum IgG binding to autoinducing peptide MsrB, FadB, EsxA, Pbp2, FadB, SspB, or SodA was very low in SABSI. This marker panel discriminated early SABSI from controls with 95% sensitivity and 100% specificity according to random forest prediction. This holds promise for patient stratification according to their risk of S. aureus infection, underlines the protective function of the adaptive immune system, and encourages further efforts in the development of a vaccine against S. aureus. IMPORTANCE S. aureus sepsis has a high complication and mortality rate. Given the limited therapeutic possibilities, effective prevention strategies, e.g., a vaccine, or the early identification of high-risk patients would be important but are not available. Our study showed an acute-phase response in patients with S. aureus bloodstream infection and evidence that lipoproteins are downregulated in plasma. Using immunoproteomics, stratification of patients appears to be achievable, since at the early stages of systemic S. aureus infection patients had low preexisting anti-S. aureus antibody levels. This strengthens the notion that a robust immune memory for S. aureus protects against infections with the pathogen.
format	article
author	Stephan Michalik Nandakumar Sundaramoorthy Annette Murr Maren Depke Uwe Völker Barbara M. Bröker Hege Vangstein Aamot Frank Schmidt
author_facet	Stephan Michalik Nandakumar Sundaramoorthy Annette Murr Maren Depke Uwe Völker Barbara M. Bröker Hege Vangstein Aamot Frank Schmidt
author_sort	Stephan Michalik
title	Early-Stage <italic toggle="yes">Staphylococcus aureus</italic> Bloodstream Infection Causes Changes in the Concentrations of Lipoproteins and Acute-Phase Proteins and Is Associated with Low Antibody Titers against Bacterial Virulence Factors
title_short	Early-Stage <italic toggle="yes">Staphylococcus aureus</italic> Bloodstream Infection Causes Changes in the Concentrations of Lipoproteins and Acute-Phase Proteins and Is Associated with Low Antibody Titers against Bacterial Virulence Factors
title_full	Early-Stage <italic toggle="yes">Staphylococcus aureus</italic> Bloodstream Infection Causes Changes in the Concentrations of Lipoproteins and Acute-Phase Proteins and Is Associated with Low Antibody Titers against Bacterial Virulence Factors
title_fullStr	Early-Stage <italic toggle="yes">Staphylococcus aureus</italic> Bloodstream Infection Causes Changes in the Concentrations of Lipoproteins and Acute-Phase Proteins and Is Associated with Low Antibody Titers against Bacterial Virulence Factors
title_full_unstemmed	Early-Stage <italic toggle="yes">Staphylococcus aureus</italic> Bloodstream Infection Causes Changes in the Concentrations of Lipoproteins and Acute-Phase Proteins and Is Associated with Low Antibody Titers against Bacterial Virulence Factors
title_sort	early-stage <italic toggle="yes">staphylococcus aureus</italic> bloodstream infection causes changes in the concentrations of lipoproteins and acute-phase proteins and is associated with low antibody titers against bacterial virulence factors
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/3572e81656174a26a0de9cae2d5fb482
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Early-Stage <italic toggle="yes">Staphylococcus aureus</italic> Bloodstream Infection Causes Changes in the Concentrations of Lipoproteins and Acute-Phase Proteins and Is Associated with Low Antibody Titers against Bacterial Virulence Factors

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