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A matrix form of fibronectin mediates enhanced binding of Streptococcus pyogenes to host tissue
1Department of Bacteriology, Institute of Medical Science, University of Tokyo, Tokyo 108, Japan. okada@ims.u-tokyo.ac.jp
Abstract:
The pathogenic Gram-positive bacterium Streptococcus pyogenes (group A streptococcus) binds to fibronectin via protein F. In this study, we have investigated the binding properties of protein F to various multimeric tissue forms of fibronectin that appear on cell surfaces and in the extracellular matrix. We show that binding of S. pyogenes through protein F is more efficient to an in vitro-derived polymerized form of fibronectin (superfibronectin) than to soluble fibronectin immobilized in a solid phase. In addition, Chinese hamster ovary cells overexpressing the alpha5beta1 integrin produced an increased amount of a fibronectin matrix and consequently bound a higher number of S. pyogenes cells. Inhibition and direct binding assays using purified proteins demonstrated that binding to a fibronectin matrix involved both domains of protein F (UR and RD2) that have previously been implicated in interactions with fibronectin. Using intact S. pyogenes bacteria in which various domains of protein F were expressed as hybrids with the surface-exposed region of an unrelated protein, we revealed that, in contrast to the predominantly UR-mediated binding to soluble fibronectin, the maximal binding to the fibronectin matrix required RD2 in addition to UR. Since in some infections S. pyogenes may initially encounter a matrix form of fibronectin, these results suggest that UR and RD2 may be important for the initiation of streptococcal infectious processes.
Insights
Streptococcus pyogenes binding to fibronectin is more efficient to matrix forms. Protein F domains UR and RD2 are crucial for this interaction, potentially aiding infection initiation.
Area of Science:
- Microbiology
- Cell Biology
- Biochemistry
Background:
- Streptococcus pyogenes (group A streptococcus) is a pathogenic bacterium.
- Protein F mediates the binding of S. pyogenes to fibronectin.
- Fibronectin exists in soluble and multimeric tissue forms.
Purpose of the Study:
- Investigate the binding properties of S. pyogenes protein F to various fibronectin tissue forms.
- Determine the role of specific protein F domains in binding to fibronectin matrices.
Main Methods:
- Compared S. pyogenes binding to soluble and polymerized fibronectin (superfibronectin).
- Utilized Chinese hamster ovary cells overexpressing alpha5beta1 integrin to study fibronectin matrix formation.
- Employed inhibition and direct binding assays with purified proteins.
- Constructed hybrid proteins to assess the function of protein F domains.
Main Results:
- S. pyogenes binding via protein F was more efficient to superfibronectin than soluble fibronectin.
- Increased fibronectin matrix production by cells overexpressing alpha5beta1 integrin led to higher bacterial binding.
- Binding to fibronectin matrix involved both UR and RD2 domains of protein F.
- Maximal binding to fibronectin matrix required both UR and RD2 domains, unlike UR-mediated binding to soluble fibronectin.
Conclusions:
- The interaction of S. pyogenes with fibronectin matrices is more complex than with soluble fibronectin.
- Both UR and RD2 domains of protein F are essential for efficient binding to fibronectin matrices.
- These findings suggest that UR and RD2 domains play a significant role in the initiation of streptococcal infections by facilitating binding to host fibronectin matrices.