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

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

Psychometric Properties of the 25-Item Connor-Davison Resilience Scale: Preliminary Data for a Romanian Military Population

The following study is aimed at investigating the construct validity of the 25-item Connor-Davidson Resilience Scale (CD-RISC 25) on a Romanian military population. The exploratory factor analysis was conducted on 434 male military participants, aged between 24 and 50 years (M = 34.83, S.D. = 6.14) and the confirmatory factor analysis was conducted on a sample of 679 military participants, of 605 men and 74 women, aged between 18 and 59 years (M = 38.37, S.D. = 9.07). Factor analysis of the scale showed it to be a bidimensional, rather than a multidimensional instrument, as the original five-factor structure was not replicated in this military Romanian sample. Moreover, EFAs suggested that a 14-item bidimensional model should be retained and CFA confirmed that this model fit the data best

Coupling laser induced photodissociation in the visible range with mass spectrometry for improved quantification of Staphylococcus aureus toxins

Development of a HPLC-LID/MS method after chromophore derivatizationStudy developed on the 5 main entero- toxins of Staphylococcus aureusToxins seen and/or quantified in strain

Coupling laser induced photodissociation in the visible range with mass spectrometry for improved quantification of Staphylococcus aureus toxins

Development of a HPLC-LID/MS method after chromophore derivatizationStudy developed on the 5 main entero- toxins of Staphylococcus aureusToxins seen and/or quantified in strain

Coupling laser induced photodissociation in the visible range with mass spectrometry for improved quantification of Staphylococcus aureus toxins

Development of a HPLC-LID/MS method after chromophore derivatizationStudy developed on the 5 main entero- toxins of Staphylococcus aureusToxins seen and/or quantified in strain

Multiplexed detection and quantification of the protein effectors of antibiotic resistance in clinical strains of Pseudomonas aeruginosa and Enterobacteriaceae by Scout-MRM – Application to positive blood cultures

International audienc

Fast and accurate identification and antibiotic resistance profiling of micro-organisms in blood cultures by SWATH DIA proteomics

International audienc

Fast and accurate identification and antibiotic resistance profiling of micro-organisms in blood cultures by SWATH DIA proteomics

International audienc

Fast and accurate identification and antibiotic resistance profiling of micro-organisms in blood cultures by SWATH-MS proteomics

International audienceToday, approximately 1.3 million people die each year worldwide from bacterial antimicrobial resistance (AMR). AMR is of great concern in the context of bloodstream infections (BSIs) when it evolves into sepsis. If MALDI-TOF has markedly shortened the delay of the pathogen identification step, AMR evaluation is still based on growth tests in the presence of antibiotics. The latter, negatively impacts the diagnosis turnaround time, thus the administration to the patient of active antimicrobial agents. With the aim of streamlining this turnaround time to less than an hour from a positive blood culture, the LC/SWATH-MS sensitivity and specificity performances were evaluated to concomitantly provide the identity and antibiotic resistance profile of pathogens related to BSIs based on peptide surrogates