Defining Host Responses during Systemic Bacterial Infection through Construction of a Murine Organ Proteome Atlas.

Cell Systems
John D LapekDavid J Gonzalez

Abstract

Group A Streptococcus (GAS) remains one of the top 10 deadliest human pathogens worldwide despite its sensitivity to penicillin. Although the most common GAS infection is pharyngitis (strep throat), it also causes life-threatening systemic infections. A series of complex networks between host and pathogen drive invasive infections, which have not been comprehensively mapped. Attempting to map these interactions, we examined organ-level protein dynamics using a mouse model of systemic GAS infection. We quantified over 11,000 proteins, defining organ-specific markers for all analyzed tissues. From this analysis, an atlas of dynamically regulated proteins and pathways was constructed. Through statistical methods, we narrowed organ-specific markers of infection to 34 from the defined atlas. We show these markers are trackable in blood of infected mice, and a subset has been observed in plasma samples from GAS-infected clinical patients. This proteomics-based strategy provides insight into host defense responses, establishes potentially useful targets for therapeutic intervention, and presents biomarkers for determining affected organs during bacterial infection.

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Citations

Jul 3, 2019·Molecular & Cellular Proteomics : MCP·Hao Q TranAndrew T Gewirtz
Jan 30, 2020·Genome Research·Robert H MillsDavid J Gonzalez
May 22, 2019·Nature Cell Biology·Stephanie GraingerDavid Traver
Feb 9, 2019·Blood·Raghavendra Palankar, Andreas Greinacher
Nov 11, 2020·Nature Reviews. Genetics·Erick ArmingolNathan E Lewis
Sep 1, 2019·Molecular & Cellular Proteomics : MCP·Hao Q TranAndrew T Gewirtz
Feb 25, 2021·Nature Communications·Fatemeh AskarianGustav Vaaje-Kolstad

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