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Updated: Jul 17, 2026
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A Fluorescence-based Method to Study Bacterial Gene Regulation in Infected Tissues
Published on: February 19, 2019
Staphylococcus aureus protein A activates TACE through EGFR-dependent signaling
Marisa I Gómez1, Maghnus O Seaghdha, Alice S Prince
1Department of Pediatrics and Pharmacology, College of Physicians & Surgeons, Columbia University, New York, NY 10032, USA. asp7@columbia.edu
The EMBO Journal
|January 27, 2007
Summary
Staphylococcus aureus protein A activates immune signaling by mimicking TNF-alpha and shedding TNFR1. A novel interaction with EGFR regulates this shedding process.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Staphylococcus aureus protein A is a complex virulence factor.
- Protein A interacts with eukaryotic targets, particularly immune cells.
- It mimics TNF-alpha to activate TNFR1 and downstream signaling.
- Protein A also induces TNFR1 shedding, limiting TNF-alpha signaling.
Purpose of the Study:
- To characterize the signaling pathway of TNFR1 shedding.
- To identify protein A mutants affecting TNFR1 shedding.
- To elucidate the interaction between protein A and TNFR1 sheddase.
Main Methods:
- Characterization of signaling pathways.
- Identification and analysis of protein A mutants.
- Investigation of protein-protein interactions using molecular biology techniques.
- Analysis of signaling cascades involving EGFR, TACE, c-Src, and erk1/2.
Main Results:
- Protein A activates TNFR1 signaling and shedding.
- Specific protein A mutants activated TNFR1 signaling but not TACE (TNFR1 sheddase).
- TACE activation depended on protein A's IgG-binding domain interacting with EGFR.
- This interaction initiated a c-Src-erk1/2-mediated cascade leading to TACE phosphorylation.
- EGFR autocrine activation and TGF-alpha were not required for TNFR1 shedding.
Conclusions:
- Staphylococcus aureus utilizes protein A to manipulate TNFR1 shedding via EGFR.
- This interaction regulates the availability of TNFR1 on immune and mucosal cells.
- The findings reveal a novel mechanism of bacterial immune evasion.
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