Fibronectin binding protein A (FnBPA) is a '' Staphylococcus aureus''

MSCRAMM MSCRAMM (acronym for "microbial surface components recognizing adhesive matrix molecules") adhesin proteins mediate the initial attachment of bacteria to host tissue, providing a critical step to establish infection. Examples include protein A, cl ...

cell surface-bound protein that binds to both

fibronectin Fibronectin is a high- molecular weight (~500-~600 kDa) glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. Fibronectin also binds to other extracellular matrix proteins such as collage ...

and

fibrinogen Fibrinogen (factor I) is a glycoprotein complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted enzymatically by thrombin to fibrin and then to a fibrin-based blood cl ...

. It is an adhesin which enables ''Staphylococcus aureus'' (''S. aureus'') to adhere to host cells of another organism, and an

invasin Invasins are a class of proteins associated with the penetration of pathogens into host cells. Invasins play a role in promoting entry during the initial stage of infection. In 2007, Als3 was identified as a fungal invasion allowing ''Candida alb ...

facilitating its internalisation into these cells. This is true over a range of different cell types. 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

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 Microfilaments, also called actin filaments, are protein filaments in the cytoplasm of eukaryotic cells that form part of the cytoskeleton. They are primarily composed of polymers of actin, but are modified by and interact with numerous other ...

, 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 Osteomyelitis (OM) is an infection of bone. Symptoms may include pain in a specific bone with overlying redness, fever, and weakness. The long bones of the arms and legs are most commonly involved in children e.g. the femur and humerus, while the ...

, and is the predominant adhesin for adherence to

osteoblasts Osteoblasts (from the Greek combining forms for "bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cells with a single nucleus that synthesize bone. However, in the process of bone formation, osteoblasts function ...

, 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

{{Toxins Blood proteins