Proteomic atlas of organ vasculopathies triggered by Staphylococcus aureus sepsis

Alejandro Gómez Toledo, Gregory Golden, Alexandre Rosa Campos, Hector Cuello, James Sorrentino, Nathan Lewis, Nissi Varki, Victor Nizet, Jeffrey W. Smith and Jeffrey D. Esko ()
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Alejandro Gómez Toledo: University of California, San Diego
Gregory Golden: University of California, San Diego
Alexandre Rosa Campos: Proteomics Core Facility, Sanford-Burnham-Prebys Medical Discovery Institute
Hector Cuello: Quilmes National University
James Sorrentino: University of California, San Diego
Nathan Lewis: University of California, San Diego
Nissi Varki: University of California, San Diego
Victor Nizet: University of California, San Diego
Jeffrey W. Smith: The Cancer Center and The Inflammatory and Infectious Disease Center, Sanford-Burnham-Prebys Medical Discovery Institute
Jeffrey D. Esko: University of California, San Diego

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-12672-x

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