Host Proteome Remodeling During Group A Streptococcus Skin Infection

Group A Streptococcus (Streptococcus pyogenes, GAS) is a bacterial pathogen that commonly causes local infections in humans and can lead to invasive diseases. GAS infections trigger complex host immune and tissue responses, yet how these processes are coordinated over time and across different tissues remains poorly understood. To explore the spectrum of GAS infection, we examined responses in a skin infection model at multiple proteome levels, characterizing local and distant tissues with variable infection responses. We map changes in canonical innate and adaptive immune signaling while uncovering new mechanisms in the context of skin infection. We uncover the robust and time-dependent expression of one family of proteins, chitinase-like proteins, that coincides with immune cell infiltration of local tissues. Because immunomodulatory networks are tightly regulated through post-translational modifications, we integrated global proteomic data with cytokine signaling and key phosphoproteome changes. This analysis revealed correlations between mTOR and kinase signaling pathways that diverge at local and systemic tissues. Our systems-based approach provides a rigorous evaluation of a GAS skin infection, characterizing host proteome remodeling across experimental groups and individual mice.