Iron-regulated surface determinant protein A (IsdA) (IsdA)

Iron-regulated surface determinant protein A (IsdA) is a multifunctional cell wall-anchored surface protein of Staphylococcus aureus that plays a critical role in the bacterium's survival and pathogenesis within the host (UniProt Q2FHV1). It is a key component of the iron-regulated surface determinant (Isd) system, which scavenges heme-iron from host hemoproteins to support bacterial growth under iron-limited conditions (PubMed 18227165). Beyond nutrient acquisition, IsdA serves as a broad-spectrum adhesin, binding to host extracellular matrix proteins like fibrinogen and fibronectin to facilitate tissue attachment and nasal colonization (PubMed 14982642). The protein also contributes to immune evasion by decreasing bacterial surface hydrophobicity, providing resistance against antimicrobial fatty acids and host peptides such as beta-defensins (Cell Host Microbe 2007). Additionally, IsdA acts as a protease inhibitor that protects the bacterium from the bactericidal activity of apolactoferrin (PubMed 18227165). Because of its essential roles in virulence and its accessibility on the bacterial surface, IsdA is a prominent target for the development of vaccines and therapeutic monoclonal antibodies (PubMed 30487231).

Other names

Fur-regulated protein AStaphylococcal transferrin-binding protein AfrpAstbAHeme transporter IsdAIron-regulated heme-iron binding proteinLPXTG-anchored heme-scavenging protein IsdA

Inhibition of heme binding and transport, blocking of bacterial adhesion to host tissues, and enhancement of opsonophagocytosis through Fc-mediated effector functions.