Targeted proteomics links virulence factor expression with clinical severity in staphylococcal pneumonia

Frontiers in Cellular and Infection Microbiology

Cellular and Infection Microbiology

Mariane Pivard¹  Florence Couzon¹  Karen Moreau¹  Sylvère Bastien¹  Anne Tristan²  François Vandenesch²  Jean-Philippe Rasigade²  Benjamin Youenou³  Iulia Macavei⁴  Nicolas Mouton⁴  Jérôme Lemoine⁴  Romain Carrière⁴ 

[1] CIRI, Centre International de Recherche en Infectiologie, Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, Centre National de la Recherche Scientifique (CNRS), UMR5308, École Normale Supérieure (ENS) de Lyon, Lyon, France;CIRI, Centre International de Recherche en Infectiologie, Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, Centre National de la Recherche Scientifique (CNRS), UMR5308, École Normale Supérieure (ENS) de Lyon, Lyon, France;Centre National de Référence des Staphylocoques, Institut des agents infectieux, Hospices Civils de Lyon, Lyon, France;Centre National de Référence des Staphylocoques, Institut des agents infectieux, Hospices Civils de Lyon, Lyon, France;Institut des Sciences Analytiques, Université de Lyon, Université Claude Bernard Lyon 1, Centre National de la Recherche Scientifique (CNRS), UMR 5280, Villeurbanne, France;

关键词: Staphylococcus aureus;    community-acquired pneumonia (CAP);    panton valentine leucocidin;    tandem mass spectrometer;    multiple reaction monitoring (MRM);   

DOI  :  10.3389/fcimb.2023.1162617

 received in 2023-02-09, accepted in 2023-03-20,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionThe 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.MethodsWe 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.ResultsWe 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.DiscussionThese 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.

【 授权许可】

Unknown   
Copyright © 2023 Pivard, Bastien, Macavei, Mouton, Rasigade, Couzon, Youenou, Tristan, Carrière, Moreau, Lemoine and Vandenesch