Targeted proteomics links virulence factor expression with clinical severity in staphylococcal pneumonia
Copyright © 2023 Pivard, Bastien, Macavei, Mouton, Rasigade, Couzon, Youenou, Tristan, Carrière, Moreau, Lemoine and Vandenesch..
Introduction: The bacterial pathogen Staphylococcus aureus harbors numerous virulence factors that impact infection severity. Beyond virulence gene presence or absence, the expression level of virulence proteins is known to vary across S. aureus lineages and isolates. However, the impact of expression level on severity is poorly understood due to the lack of high-throughput quantification methods of virulence proteins.
Methods: We present a targeted proteomic approach able to monitor 42 staphylococcal proteins in a single experiment. Using this approach, we compared the quantitative virulomes of 136 S. aureus isolates from a nationwide cohort of French patients with severe community-acquired staphylococcal pneumonia, all requiring intensive care. We used multivariable regression models adjusted for patient baseline health (Charlson comorbidity score) to identify the virulence factors whose in vitro expression level predicted pneumonia severity markers, namely leukopenia and hemoptysis, as well as patient survival.
Results: We found that leukopenia was predicted by higher expression of HlgB, Nuc, and Tsst-1 and lower expression of BlaI and HlgC, while hemoptysis was predicted by higher expression of BlaZ and HlgB and lower expression of HlgC. Strikingly, mortality was independently predicted in a dose-dependent fashion by a single phage-encoded virulence factor, the Panton-Valentine leucocidin (PVL), both in logistic (OR 1.28; 95%CI[1.02;1.60]) and survival (HR 1.15; 95%CI[1.02;1.30]) regression models.
Discussion: These findings demonstrate that the in vitro expression level of virulence factors can be correlated with infection severity using targeted proteomics, a method that may be adapted to other bacterial pathogens.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Frontiers in cellular and infection microbiology - 13(2023) vom: 06., Seite 1162617 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Pivard, Mariane [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 21.04.2023 Date Revised 21.04.2023 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.3389/fcimb.2023.1162617 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Targeted proteomics links virulence factor expression with clinical severity in staphylococcal pneumonia |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 Pivard, Bastien, Macavei, Mouton, Rasigade, Couzon, Youenou, Tristan, Carrière, Moreau, Lemoine and Vandenesch. | ||
| 520 | |a Introduction: The bacterial pathogen Staphylococcus aureus harbors numerous virulence factors that impact infection severity. Beyond virulence gene presence or absence, the expression level of virulence proteins is known to vary across S. aureus lineages and isolates. However, the impact of expression level on severity is poorly understood due to the lack of high-throughput quantification methods of virulence proteins | ||
| 520 | |a Methods: We present a targeted proteomic approach able to monitor 42 staphylococcal proteins in a single experiment. Using this approach, we compared the quantitative virulomes of 136 S. aureus isolates from a nationwide cohort of French patients with severe community-acquired staphylococcal pneumonia, all requiring intensive care. We used multivariable regression models adjusted for patient baseline health (Charlson comorbidity score) to identify the virulence factors whose in vitro expression level predicted pneumonia severity markers, namely leukopenia and hemoptysis, as well as patient survival | ||
| 520 | |a Results: We found that leukopenia was predicted by higher expression of HlgB, Nuc, and Tsst-1 and lower expression of BlaI and HlgC, while hemoptysis was predicted by higher expression of BlaZ and HlgB and lower expression of HlgC. Strikingly, mortality was independently predicted in a dose-dependent fashion by a single phage-encoded virulence factor, the Panton-Valentine leucocidin (PVL), both in logistic (OR 1.28; 95%CI[1.02;1.60]) and survival (HR 1.15; 95%CI[1.02;1.30]) regression models | ||
| 520 | |a Discussion: These findings demonstrate that the in vitro expression level of virulence factors can be correlated with infection severity using targeted proteomics, a method that may be adapted to other bacterial pathogens | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Staphylococcus aureus | |
| 650 | 4 | |a community-acquired pneumonia (CAP) | |
| 650 | 4 | |a multiple reaction monitoring (MRM) | |
| 650 | 4 | |a panton valentine leucocidin | |
| 650 | 4 | |a tandem mass spectrometer | |
| 650 | 7 | |a Virulence Factors |2 NLM | |
| 650 | 7 | |a Exotoxins |2 NLM | |
| 650 | 7 | |a Leukocidins |2 NLM | |
| 700 | 1 | |a Bastien, Sylvère |e verfasserin |4 aut | |
| 700 | 1 | |a Macavei, Iulia |e verfasserin |4 aut | |
| 700 | 1 | |a Mouton, Nicolas |e verfasserin |4 aut | |
| 700 | 1 | |a Rasigade, Jean-Philippe |e verfasserin |4 aut | |
| 700 | 1 | |a Couzon, Florence |e verfasserin |4 aut | |
| 700 | 1 | |a Youenou, Benjamin |e verfasserin |4 aut | |
| 700 | 1 | |a Tristan, Anne |e verfasserin |4 aut | |
| 700 | 1 | |a Carrière, Romain |e verfasserin |4 aut | |
| 700 | 1 | |a Moreau, Karen |e verfasserin |4 aut | |
| 700 | 1 | |a Lemoine, Jérôme |e verfasserin |4 aut | |
| 700 | 1 | |a Vandenesch, François |e verfasserin |4 aut | |
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