Fibronectin binding protein A explained

Fibronectin binding protein A (FnBPA) is a Staphylococcus aureus^[1] MSCRAMM cell surface-bound protein that binds to both fibronectin and fibrinogen.

It is an adhesin which enables Staphylococcus aureus (S. aureus) to adhere to host cells of another organism, and an invasin facilitating its internalisation into these cells.^[2] This is true over a range of different cell types.^{[3] [4]} The FnBP alone is capable of providing this invasive property, without the requirement of co-receptors. Even FnBP coated beads have been shown to become internalised into cells

S. aureus is able to bind to host cells in the absence of the FnBP, but its adherence and invasive properties are much reduced (up to a 500-fold decrease in number of internalised cells)

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 ^[5]

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.^[6] 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.^[7]

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.^[8]

Notes and References

1. Jönsson K, Signäs C, Müller HP, Lindberg M . Two different genes encode fibronectin binding proteins in Staphylococcus aureus. The complete nucleotide sequence and characterization of the second gene . European Journal of Biochemistry . 202 . 3 . 1041–8 . December 1991 . 1837266 . 10.1111/j.1432-1033.1991.tb16468.x . free .
2. Sinha B, Francois P, Que YA, Hussain M, Heilmann C, Moreillon P, Lew D, Krause KH, Peters G, Herrmann M . Heterologously Expressed Staphylococcus aureus Fibronectin-Binding Proteins Are Sufficient for Invasion of Host Cells . Infect. Immun. . 2000 . 11083807 . 68 . 12 . 6871–8 . 97792 . 10.1128/iai.68.12.6871-6878.2000.
3. Jett BD, Gilmore MS . Internalization of Staphylococcus aureus by Human Corneal Epithelial Cells: Role of Bacterial Fibronectin-Binding Protein and Host Cell Factors . Infect. Immun. . 2002 . 12117986 . 70 . 8 . 4697–700 . 128182 . 10.1128/iai.70.8.4697-4700.2002.
4. Ahmed S, Meghji S, Williams RJ, Henderson B, Brock JH, Nair SP . Staphylococcus aureus Fibronectin Binding Proteins Are Essential for Internalization by Osteoblasts but Do Not Account for Differences in Intracellular Levels of Bacteria . Infect. Immun. . 2001 . 11292701 . 69 . 5 . 2872–7 . 10.1128/IAI.69.5.2872-2877.2001 . 98237.
5. Williams RJ, Henderson B, Nair SP . 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 . 2002 . 12055657 . 70 . 5 . 416–21 . 10.1007/s00223-001-2073-z.
6. Huveneers S, Truong H, Fässler R, Sonnenberg A, Danen EH . Binding of soluble fibronectin to integrin alpha5 beta1 - link to focal adhesion redistribution and contractile shape . J Cell Sci . 2008 . 18611961 . 121 . Pt 15 . 2452–62 . 10.1242/jcs.033001. free . 1887/68178 . free .
7. Menzies BE. . The role of fibronectin binding proteins in the pathogenesis of Staphylococcus aureus infections . Current Opinion in Infectious Diseases . 2003 . 12821812 . 16 . 3 . 225–9 . 10.1097/00001432-200306000-00007.
8. McCourt. Jennifer. O'Halloran. Dara P.. McCarthy. Hannah. O'Gara. James P.. Geoghegan. Joan A.. Fibronectin-binding proteins are required for biofilm formation by community-associated methicillin-resistant Staphylococcus aureus strain LAC. FEMS Microbiology Letters. April 2014. 353. 2. 157–64. 10.1111/1574-6968.12424. 24628034. free. 10379/12737. free.