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Updated: Jun 23, 2026
Invasion of Human Cells by a Bacterial Pathogen
Published on: March 21, 2011
Capturing host-pathogen interactions by protein microarrays: identification of novel streptococcal proteins binding
Immaculada Margarit1, Stefano Bonacci, Giampiero Pietrocola
1Novartis Vaccines & Diagnostics, Siena, Italy. immaculada.margarit_y_ros@novartis.com
Abstract:
Microbial pathogen entry and survival in the host is mediated by a network of molecular interactions between the two partners, which has been the subject of many research efforts. A complex picture is emerging in which host-pathogen crosstalk involves a high number of proteins, often with redundant functions. In the present study, we investigated the potential of protein microarrays to simultaneously scan interactions between surface proteins from two main human streptococcal pathogens, Streptococcus pyogenes and Streptococcus agalactiae, and three human ligands, fibronectin, fibrinogen, and C4 binding protein, known to play an important role in streptococcal pathogenesis. By using this technology, we confirmed interactions described in the literature and detected a novel set of streptococcal proteins with binding capacities for the human ligands. The observations were validated by Western blot and ELISA techniques. Three of the newly identified proteins were isoforms of a group B streptococcus-secreted component named Fib and displayed differential binding capacities for fibronectin, fibrinogen, and C4BP. The protein regions involved in the interaction with each ligand were identified by constructing fragments of one of the Fib variants. The approach proved valuable for the acquisition of novel insights into the complex network of protein-protein interactions occurring during microbial infection.
Insights
Protein microarrays reveal new interactions between streptococcal pathogens and human ligands, uncovering novel proteins involved in host-pathogen binding and infection pathways.
Area of Science:
- Microbiology
- Molecular Biology
- Immunology
Background:
- Host-pathogen interactions are crucial for microbial survival and pathogenesis.
- Understanding these molecular networks is key to developing new therapeutic strategies.
- Streptococcal pathogens like Streptococcus pyogenes and Streptococcus agalactiae engage in complex crosstalk with host proteins.
Purpose of the Study:
- To investigate protein-protein interactions between streptococcal surface proteins and human ligands using protein microarrays.
- To identify novel streptococcal proteins involved in binding to fibronectin, fibrinogen, and C4 binding protein.
- To characterize the binding specificities and interaction regions of newly identified streptococcal proteins.
Main Methods:
- Utilized protein microarrays for high-throughput screening of interactions.
- Confirmed identified interactions using Western blot and ELISA assays.
- Employed protein fragment construction to map interaction domains.
Main Results:
- Confirmed known interactions between streptococcal proteins and human ligands.
- Discovered a novel set of streptococcal proteins that bind to fibronectin, fibrinogen, and C4 binding protein.
- Identified three isoforms of the Fib protein with differential ligand binding capacities and mapped their interaction regions.
Conclusions:
- Protein microarrays are effective tools for dissecting complex host-pathogen protein interaction networks.
- Novel streptococcal proteins, including Fib isoforms, have been identified with significant roles in pathogen adherence and pathogenesis.
- This study provides valuable insights into the molecular mechanisms underlying streptococcal infections.
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