Fibronectin binding protein A

Structure

The FnBP inserts into the cell wall of S. aureus by means of a C-terminal LPXTG anchor. Two fibronectin binding domains have been identified - one is present in the C-terminal D repeat region, and one in the N-terminal A region

Mechanism

The fibronectin binding protein is able to bind fibronectin present in the extracellular matrix. Similarly, the α5β1 integrin present on host cells also binds fibronectin to create a link to its actin cytoskeleton, binding via the Arg-Gly-Asp (RGD) motif present in fibronectin. Fibronectin is able to act as a ‘bridge’ between S. aureus and the host cell, with both S. aureus and the host cell binding at either end of the molecule, and therefore facilitate adherence.

Clinical significance

The FnBP is involved in adherence to a wide range of mammalian cells and is hence implicated in various infections.

It is implicated in the pathogenesis of osteomyelitis, and is the predominant adhesin for adherence to osteoblasts, a cell type present in large quantities within bone. Few S. aureus cells become internalised into osteoblasts in the absence of the FnBP

FnBPs are essential in the formation of biofilms by community-associated methicillin-resistant Staphylococcus aureus strain LAC. They are specifically involved in primary attachment.

References

References

1. (December 1991). "Two different genes encode fibronectin binding proteins in Staphylococcus aureus. The complete nucleotide sequence and characterization of the second gene". European Journal of Biochemistry.
2. (2000). "Heterologously Expressed Staphylococcus aureus Fibronectin-Binding Proteins Are Sufficient for Invasion of Host Cells". Infect. Immun..
3. (2002). "Internalization of Staphylococcus aureus by Human Corneal Epithelial Cells: Role of Bacterial Fibronectin-Binding Protein and Host Cell Factors". Infect. Immun..
4. (2001). "Staphylococcus aureus Fibronectin Binding Proteins Are Essential for Internalization by Osteoblasts but Do Not Account for Differences in Intracellular Levels of Bacteria". Infect. Immun..
5. (2002). "Staphylococcus aureus fibronectin binding proteins A and B possess a second fibronectin binding region that may have biological relevance to bone tissues". Calcif Tissue Int.
6. (2008). "Binding of soluble fibronectin to integrin alpha5 beta1 - link to focal adhesion redistribution and contractile shape". J Cell Sci.
7. Menzies BE.. (2003). "The role of fibronectin binding proteins in the pathogenesis of Staphylococcus aureus infections". Current Opinion in Infectious Diseases.
8. (April 2014). "Fibronectin-binding proteins are required for biofilm formation by community-associated methicillin-resistant Staphylococcus aureus strain LAC". FEMS Microbiology Letters.