Proteomics identifies a convergent innate response to infective endocarditis and extensive proteolysis in vegetation components

作者: Daniel R. Martin , James C. Witten , Carmela D. Tan , E. Rene Rodriguez , Eugene H. Blackstone

DOI: 10.1172/JCI.INSIGHT.135317

关键词: ProteasesProteomicsProteomeInfective endocarditisBiologyVirulenceProteolysisTerminal amine isotopic labeling of substratesPathogenMicrobiology

摘要: Infective endocarditis is a life-threatening infection of heart valves and adjacent structures characterized by vegetations on other endocardial surfaces, with tissue destruction risk embolization. We used high-resolution mass spectrometry to define the proteome staphylococcal non-staphylococcal Terminal Amine Isotopic Labeling Substrates (TAILS) their proteolytic landscapes. These approaches identified over 2000 human proteins in vegetations. Individual vegetation proteomes demonstrated comparable profiles quantitatively major constituents that overlapped serum, platelet, neutrophil proteomes. Staphylococcal resembled one another more than TAILS extensive proteolysis within vegetations, numerous previously undescribed cleavages. Several proteases pathogen-specific proteins, including virulence factors, were most Proteolytic peptides fibronectin complement C3 as potential infective biomarkers. Overlap suggests convergent thrombotic immune response diverse pathogens. However, differences between internal variance group indicate additional pathogen- or patient-specific effects exist. Pervasive components may arise from vegetation-intrinsic destabilize contributing embolism.

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