Staphylococcus aureus Iron-regulated surface determinant protein B – Vitronectin interaction (IsdB–VTN interaction)

Iron-regulated surface determinant protein B (IsdB) is a cell-wall-anchored protein of Staphylococcus aureus that plays a critical role in nutrient acquisition and host colonization (Singh et al., 2010, J. Biol. Chem.). While primarily recognized as a high-affinity receptor for hemoglobin to facilitate iron uptake, IsdB also functions as an adhesin by binding to the host extracellular matrix protein vitronectin (UniProt Q7A655). This interaction promotes the attachment of S. aureus to human cells and contributes to the pathogenesis of invasive infections such as bacteremia and endocarditis. IsdB has been a prominent target for vaccine development, most notably the V710 vaccine, which aimed to induce protective antibodies to block its functions (Fowler et al., 2013, JAMA). However, clinical trials revealed significant safety concerns, including increased mortality in vaccinated individuals who subsequently developed S. aureus infections, leading to the discontinuation of the lead candidate. Despite these challenges, the IsdB–vitronectin interaction remains a subject of study for understanding bacterial virulence and developing alternative anti-infective strategies. The interaction is specifically mediated by the NEAT (Near Iron Transporter) domains of IsdB, which are also involved in heme binding. Targeting this interaction could potentially prevent bacterial dissemination and reduce the severity of staphylococcal disease.

Other names

IsdB-vitronectin bindingS. aureus IsdB-VTN complexHeme-binding protein IsdB interaction with vitronectinStaphylococcus aureus IsdB-vitronectin adhesin complex

Inhibition of bacterial adhesion to host tissues and blockade of iron/heme acquisition by neutralizing the IsdB surface protein or its interaction with host ligands like vitronectin and hemoglobin (Fowler et al., 2013, JAMA).