The Multivalent Role of Fibronectin-Binding Proteins A and B (FnBPA and FnBPB) of Staphylococcus aureus in Host Infections

Abstract

Staphylococcus aureus, one of the most important human pathogens, is the causative agent of several infectious diseases including sepsis, pneumonia, osteomyelitis, endocarditis and soft tissue infections. This pathogenicity is due to a multitude of virulence factors including several cell wall-anchored proteins (CWA). CWA proteins have modular structures with distinct domains binding different ligands. The majority of S. aureus strains express two CWA fibronectin (Fn)-binding adhesins FnBPA and FnBPB (Fn-binding proteins A and B), which are encoded by closely related genes. The N-terminus of FnBPA and FnBPB comprises an A domain which binds ligands such as fibrinogen, elastin and plasminogen. The A domain of FnBPB also interacts with histones and this binding results in the neutralization of the antimicrobial activity of these molecules. The C-terminal moiety of these adhesins comprises a long, intrinsically disordered domain composed of 11/10 fibronectin-binding repeats. These repetitive motifs of FnBPs promote invasion of cells that are not usually phagocytic via a mechanism by which they interact with integrin α 5 β 1 through a Fn mediated-bridge. The FnBPA and FnBPB A domains engage in homophilic cell-cell interactions and promote biofilm formation and enhance platelet aggregation. In this review we update the current understanding of the structure and functional properties of FnBPs and emphasize the role they may have in the staphylococcal infections.

Staphylococcus aureus induces neutrophil extracellular traps (NETs) and neutralizes their bactericidal potential

“…Protein A (SpA), another important CWA protein, binds to the Fc domain of IgG in an incorrect orientation which results in the protection of staphylococci from opsonophagocytosis and killing. SpA also binds to the Fab region of surface IgM located on B lymphocytes, triggering the proliferation and apoptotic collapse of adaptive immune responses [39] , [40] , [41] ( Fig. 2 ).…”

First Description of the Composition and the Functional Capabilities of the Skin Microbial Community Accompanying Severe Scabies Infestation in Humans

“…Pathogenic bacteria such as Staphylococci and Streptococci are able to adhere to human skin fibroblasts and to invade epithelial cells using a zipper model mechanism. These Gram-positive bacteria express adhesin proteins on their surfaces that interact with extracellular matrix components of the host such as fibronectin, resulting in close apposition of the epithelial cellular membrane around the entering bacteria [ 69 , 70 , 71 ] ( Supplementary File, Figure S3 ). Genes from the pathway ‘ Staphylococcus infection’ were identified in both samples from Patient A and Patient B.…”

Monoclonal Antibodies Targeting Surface-Exposed and Secreted Proteins from Staphylococci

“…CWA proteins are covalently anchored to the peptidoglycan scaffold by membrane-associated sortases. Fibronectin-binding proteins A and B (FnBPA and FnBPB) were the first proteins of S. aureus to be characterized, and they have been shown to share with clumping factor A (ClfA) the property of binding to fibrinogen with a similar mechanism [ 12 , 13 ]. FnBPA and FnBPB are also involved in plasminogen binding [ 14 ], and FnBPB interacts with additional binders, such as histones [ 15 ], and corneodesmosin [ 16 ].…”