IsdA of Staphylococcus aureus is a broad spectrum, iron-regulated adhesin.
As an important facet of host-pathogen interaction, Staphylococcus aureus has the ability to adhere to human extracellular matrix (ECM) components via a range of surface proteins. Here we have shown that IsdA has broad-spectrum ligand-binding activity, including fibrinogen and fibronectin. Mapping studies revealed a distinct domain responsible for ligand binding. This domain is present in a number of iron-regulated proteins of S. aureus and in other Gram-positive organisms. The isdA gene is only expressed in iron-limited conditions under the control of Fur and not in standard laboratory media. Such conditions occur in serum in vitro and during infection. Whole cell binding and clumping assays revealed that when the bacteria are grown under iron-limited conditions, IsdA constitutes a physiologically relevant adhesin to both fibrinogen and fibronectin. Thus for S. aureus, iron is an important marker for the host environment, to which the bacterium responds by differential regulation of at least one element of its adhesive strategy.
Department of Molecular Biology and Biotechnology, University of Sheffield, Firth Court, Western Bank, Sheffield, S10 2TN, UK.
Simon R
SR
Clarke
Michael D
MD
Wiltshire
Simon J
SJ
Foster
D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism; D002473:Cell Wall / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D017930:Genes, Reporter; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007501:Iron / Q000378:metabolism*; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D014158:Transcription, Genetic
D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D001798:Blood Proteins; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D007074:Immunoglobulin G; D012097:Repressor Proteins; C048165:adhesin, Staphylococcus aureus; C068477:ferric uptake regulating proteins, bacterial; D005340:Fibrinogen; D007501:Iron