Fibronectin binding protein A
Encyclopedia
Fibronectin binding protein A (FnBPA) is a Staphylococcus aureus
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. 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)
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.
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
It is also an important virulence factor
in S. aureus
endocarditis
.
Staphylococcus aureus
Staphylococcus aureus is a facultative anaerobic Gram-positive coccal bacterium. It is frequently found as part of the normal skin flora on the skin and nasal passages. It is estimated that 20% of the human population are long-term carriers of S. aureus. S. aureus is the most common species of...
MSCRAMM
MSCRAMM
MSCRAMM adhesin proteins mediate the initial attachment of bacteria to host tissue, providing a critical step to establish infection....
cell surface-bound protein that binds to both fibronectin
Fibronectin
Fibronectin is a high-molecular weight glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. In addition to integrins, fibronectin also binds extracellular matrix components such as collagen, fibrin and heparan sulfate proteoglycans...
and fibrinogen
Fibrinogen
Fibrinogen is a soluble plasma glycoprotein, synthesised by the liver, that is converted by thrombin into fibrin during blood coagulation. This is achieved through processes in the coagulation cascade that activate the zymogen prothrombin to the serine protease thrombin, which is responsible for...
.
It is an adhesin
Adhesin
Adhesins are cell-surface components or appendages of bacteria that facilitate bacterial adhesion or adherence to other cells or to inanimate surfaces. Adhesins are a type of virulence factor....
which enables Staphylococcus aureus (S. aureus) to adhere to host cells of another organism, and an invasin 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 regionMechanism
The fibronectin binding protein is able to bind fibronectin present in the extracellular matrix. Similarly, the α5β1 integrinAlpha-5 beta-1
α5β1 is an integrin that binds to matrix macromolecules and proteinases and thereby stimulates angiogenesis. It is composed of α5 and β1 subunits. It is the primary receptor for fibronectin...
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
Osteomyelitis
Osteomyelitis simply means an infection of the bone or bone marrow...
, 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
It is also an important virulence factor
Virulence factor
Virulence factors are molecules expressed and secreted by pathogens that enable them to achieve the following:* colonization of a niche in the host...
in S. aureus
Staphylococcus aureus
Staphylococcus aureus is a facultative anaerobic Gram-positive coccal bacterium. It is frequently found as part of the normal skin flora on the skin and nasal passages. It is estimated that 20% of the human population are long-term carriers of S. aureus. S. aureus is the most common species of...
endocarditis
Endocarditis
Endocarditis is an inflammation of the inner layer of the heart, the endocardium. It usually involves the heart valves . Other structures that may be involved include the interventricular septum, the chordae tendineae, the mural endocardium, or even on intracardiac devices...
.