ClfA

Clumping factor A (ClfA) is a surface-anchored protein of the bacterium Staphylococcus aureus and is a member of the MSCRAMM (microbial surface components recognizing adhesive matrix molecules) family. The clfA gene encodes a cell wall–associated protein that contains a C-terminal LPXTG motif, enabling covalent attachment to the peptidoglycan by sortase A, with export through the Sec pathway. The mature protein presents an N-terminal A domain, which includes ligand-binding subdomains, followed by a spacer region and a cell wall–anchoring segment.

ClfA mediates adhesion by binding fibrinogen, particularly its gamma chain, in both soluble and immobilized forms. This interaction promotes clumping of S. aureus in plasma and facilitates attachment to damaged endothelium and to platelets, contributing to the pathogen’s ability to establish infections such as endocarditis and septicemia. The binding surface on ClfA and the fibrinogen gamma chain has been studied as a model for protein–protein interactions involved in bacterial adhesion and host defense evasion.

In terms of regulation and clinical relevance, clfA expression is controlled by global regulatory networks and can be upregulated in host environments. ClfA is a focus of vaccine and therapeutic research, as antibodies targeting the A-domain can block fibrinogen binding and have been shown to reduce virulence in experimental models. As a prototypical MSCRAMM, ClfA remains a key example for understanding bacterial adhesion mechanisms and the development of anti-adhesin strategies.