Project description:Infective endocarditis, a life-threatening condition, poses significant challenges for early diagnosis and personalized treatment due to insufficient biomarkers and limited understanding of its pathophysiology. Here, we analyzed plasma and vegetation proteomes from 238 patients with infective endocarditis and 100 controls, with two external validation cohorts. We developed machine learning-based diagnostic and prognostic models for infective endocarditis, with area under the curve values of 0.98 and 0.87, respectively. Leucine-rich alpha-2-glycoprotein 1 and NADH:ubiquinone oxidoreductase subunit B4 are potential biomarkers associated with infection severity. Pathologically, protein networks characterized by glycometabolism, amino acid metabolism, and adhesion are linked to adverse events. Liver dysfunction may exacerbate the condition in patients with severe heart failure. Neutrophil extracellular traps emerge as promising therapeutic targets in Streptococcus or Staphylococcus aureus infections. Collectively, our findings provide significant insights into biomarker discovery and underlying pathophysiological mechanisms in infective endocarditis, advancing early diagnosis and personalized medicine.
Project description:S. aureus has a propensity to cause endocarditis; diabetes mellitus is a frequent underlying comorbitity in patents with S. aureus endocarditis. S. aureus Affymetrix GeneChips were used to compare S. aureus expression properties in cardiac vegatations isolated from diabetic and nondiabetic rats. S. aureus Affymetrix GeneChips were also used to compare the S. aureus expression properties of cardiac vegatations (both diabetic and nondiabetic) in comparsions to planktonic cells. Few differences were observed between the expression properties of S. aureus harvested from diabetic vs. nondiabetic cardiac vegatations. Significant differences were observed between the expression properties of S. aureus harvested from cardiac vegetations in comparison to exponential and/or stationary phase planktonically grown cells.
Project description:Mapping of transposon mutant library during growth in Brain Heart Infusion (BHI) broth and in a rat endocarditis model. The goal of this study was to identify factors that play a role in E. faecium endocarditis by selection of transposon insertion mutants that lost the capacity to cause infections.
Project description:Transcriptional profiles of cardiac valves from patients with bacterial infectious endocarditis (3 infected with Streptococcus sp. and 2 infected with Staphylococcus aureus) were compared with uninfected cardiac valves (7 patients) from patients with hemodynamic disturbing events
Project description:Infective endocarditis is a severe disease caused by the infection of heart valves and endocardium by pathogenic germ. Antimicrobial therapy and surgery remain the basis of treatment, and up to 50% of the patients require surgical replacement of the affected valves to control the infectious source. The objective of this work is to identify the existence of endotypes in a prospective cohort of patients with infective endocarditis. We performed a bulk RNA-seq form peripheral blood to cluster patients according to their transcriptomic profiles at diagnosis and during their follow-up. Clinical data, outcomes and response to surgery were assessed in a cluster-specific manner, in order to identify differences in the pathogenesis that could help to find personalized treatments and improve the outcome.