Peptide analogs to a fibronectin receptor inhibit attachment of Staphylococcus aureus to fibronectin-containing substrates.
Binding of cells of Staphylococcus aureus to fibronectin has been proposed as a mechanism of bacterial adhesion to host tissues. In this study, we have attempted to define the role of a recently identified fibronectin receptor in the adhesion of staphylococcal cells to fibronectin-containing substrates by using different receptor analogs as potential inhibitors of bacterial adherence. The results showed that synthetic peptides D1, D2, and D3, corresponding to variations of a repeated unit in the fibronectin-binding domain of the receptor, and ZZ-FR, a chimeric protein containing the fibronectin-binding domain of the receptor with the D1, D2, and D3 sequences, inhibited the attachment of staphylococcal cells to microtiter wells coated with intact fibronectin or with the 29-kilodalton amino-terminal fragment of fibronectin. The chimeric protein ZZ-FR also partially inhibited the adherence of staphylococci to human plasma clots formed in vitro but had no effect on bacterial adhesion to clots formed from fibronectin-depleted plasma. These data confirm previous reports suggesting that fibronectin may serve as a substrate for adhesion of staphylococcal cells and indicate that bacterial adhesion is mediated by the identified fibronectin receptor. Furthermore, analogs to the fibronectin receptor can be used to inhibit the adhesion of bacterial cells to these model substrates, and these analogs may be of clinical use.
Raja
R H
RH
Department of Biochemistry, University of Alabama, Birmingham 35294.
Raucci
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G
Hook
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M
D000818:Animals; D001422:Bacterial Adhesion / Q000187:drug effects*; D001777:Blood Coagulation; D002417:Cattle; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism
D005353:Fibronectins; D010455:Peptides; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic