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Proteomic atlas of organ vasculopathies triggered by Staphylococcus aureus sepsis.

  • Toledo, Alejandro Gómez
  • Golden, Gregory
  • Campos, Alexandre Rosa
  • Cuello, Hector
  • Sorrentino, James
  • Lewis, Nathan
  • Varki, Nissi
  • Nizet, Victor
  • Smith, Jeffrey W
  • Esko, Jeffrey D
Publication Date
Oct 11, 2019
eScholarship - University of California
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Sepsis is a life-threatening condition triggered by a dysregulated host response to microbial infection resulting in vascular dysfunction, organ failure and death. Here we provide a semi-quantitative atlas of the murine vascular cell-surface proteome at the organ level, and how it changes during sepsis. Using in vivo chemical labeling and high-resolution mass spectrometry, we demonstrate the presence of a vascular proteome that is perfusable and shared across multiple organs. This proteome is enriched in membrane-anchored proteins, including multiple regulators of endothelial barrier functions and innate immunity. Further, we automated our workflows and applied them to a murine model of methicillin-resistant Staphylococcus aureus (MRSA) sepsis to unravel changes during systemic inflammatory responses. We provide an organ-specific atlas of both systemic and local changes of the vascular proteome triggered by sepsis. Collectively, the data indicates that MRSA-sepsis triggers extensive proteome remodeling of the vascular cell surfaces, in a tissue-specific manner.

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