Fibronectin: a multidomain host adhesin targeted by bacterial fibronectin-binding proteins

Abstract

Fibronectin, a large and essential multidomain glycoprotein, with multiple adhesive properties, functioning as a key link between cells and their extracellular matrices, is now recognized to be the target for a large number of bacterial proteins, which are generally considered to function as bacterial adhesins. In the last decade, an avalanche of bacterial fibronectin-binding proteins (FnBPs) has been identified, and the bioinformatics, structural biology, biological function and role in the virulence of a growing number of both Gram-positive and Gram-negative proteins have begun to emerge. The evidence suggests that fibronectin has a wider biological remit than was previously thought and that bacterial FnBPs have actions over and above that of simple adhesion. This article provides an update on our current understanding of FnBPs from both Gram-negative and Gram-positive bacteria and their proposed roles in bacterial colonization, bacterial virulence and bacteria-host interactions.

Bacterial adhesion to animal tissues: protein determinants for recognition of extracellular matrix components

“…FBD5 (IPR004237) is certainly the domain having attracted the most interest (Henderson et al, 2011). It is exclusively found in the phylum Firmicutes, essentially the genera Staphylococcus and Streptococcus.…”

“…Interestingly, the ability to bind soluble fibronectin would vary from one fibronectinbinding protein (FnBP) to another; e.g. PavA cannot but Fbp54 can bind the soluble form (Henderson et al, 2011). With 1160 species, FBD3 is the most largely distributed FBD in bacteria.…”

“…Of note, the involvement of MAP (MHC class II analogous protein) domain (IPR005298) in specific binding to fibronectin remains to be ascertained. Besides FBDs, some other domains involved in fibronectin binding have been described but no pattern/profile is as yet available in databases (Henderson et al, 2011), e.g. EWYYQ motif in antigen 85B, FRLS motif in CadF (Campylobacter adhesin to fibronectin), glutamine-rich motifs in Hlp3 (HMW3-like protein) and PlpA (pneumoniae-like protein A), terminal immunoglobulin (Ig)-like repeats (IPR003343) in LigA (Leptospira immunoglobulin-like protein A) and LigB, or the motif within the 46-205 residues of Bbk32 (Borrelia burgdorferi protein encoded by locus bbk32).…”

The evolutionary origin and possible functional roles of FNIII domains in two Microbacterium aurum B8.A granular starch degrading enzymes, and in other carbohydrate acting enzymes

“…Due to the low number of recognized bacterial FNIII domains at that time, and phylogenetic analysis placing them separate from the eukaryotic domains, it was suggested that prokaryotes had acquired FNIII domains from eukaryotes [7]. All initially identified prokaryotic FNIII domains were associated with carbohydrate acting enzymes, but more recently these domains have also been identified in fibronectin binding proteins and multiple other prokaryotic protein types [8][9][10]. Our database searches showed that about 33% of all FNIII containing proteins included in SMART database (15125) [10] are from bacteria.…”

Fibronectin-binding nanoparticles for intracellular targeting addressed by B. burgdorferi BBK32 protein fragments

“…20,21 In addition, a number of studies suggested an active role of FN adsorption in cellular uptake of nonviral nanocarriers (for review, see Adler et al 22 A large amount of bacterial FN-binding protein has been identified so far; among them is BBK32, a 47 kDa surfaceexposed lipoprotein and FN-binding adhesin of Borrelia burgdorferi (B. burgdorferi). 23,24 BBK32 contains multiple FN-binding motifs located to an extended intrinsically disordered segment. 25 It was shown that the region of BBK32 comprising amino acids 147 -205 binds to the N-terminal FNI and FNIII modules, but residues 120 -147 of BBK32 protein are considered similar to the FN-binding region of SfbI protein from S. pyogenes that had been shown to bind to the GBD of FN.…”