1. Defining Host Responses during Systemic Bacterial Infection through Construction of a Murine Organ Proteome Atlas
- Author
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Lapek, John D, Mills, Robert H, Wozniak, Jacob M, Campeau, Anaamika, Fang, Ronnie H, Wei, Xiaoli, van de Groep, Kirsten, Perez-Lopez, Araceli, van Sorge, Nina M, Raffatellu, Manuela, Knight, Rob, Zhang, Liangfang, and Gonzalez, David J
- Subjects
Biochemistry and Cell Biology ,Biological Sciences ,Emerging Infectious Diseases ,Foodborne Illness ,Infectious Diseases ,Vaccine Related ,2.2 Factors relating to the physical environment ,Aetiology ,2.1 Biological and endogenous factors ,Infection ,Inflammatory and immune system ,Animals ,Bacterial Proteins ,Host-Pathogen Interactions ,Mice ,Mice ,Inbred C57BL ,Organ Specificity ,Pharyngitis ,Protein Interaction Maps ,Proteome ,Proteomics ,Sepsis ,Streptococcal Infections ,Streptococcus ,Streptococcus pyogenes ,Tandem Mass Spectrometry ,Orbitrap ,S. pyogenes ,Tandem Mass Tag ,group A Streptococcus ,multiplexed proteomics ,systemic infection ,Biochemistry and cell biology - 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.
- Published
- 2018