Trends in Microbiology
ReviewsSurface protein adhesins of Staphylococcus aureus
Section snippets
Fibronectin-binding MSCRAMMs
Fibronectin binding is a very common property of S. aureus isolates. Most strains express two related fibronectin-binding proteins, FnBPA and FnBPB, which are encoded by two closely linked genes10, 11. Studies with isogenic mutants and recombinant protein fragments show that the proteins are responsible for mediating bacterial attachment to immobilized fibronectin in vitro and contribute to the adherence of S. aureus cells to plasma clots and to ex vivo biomaterial that has been in long-term
The collagen-binding MSCRAMM
The collagen-binding protein Cna mediates bacterial adherence to collagen substrates and collagenous tissues[25]. The presence of Cna is sufficient and necessary for S. aureus cells to adhere to cartilage in vitro[26]. Antibodies against Cna inhibit bacterial binding to collagen and block bacterial adherence to cartilage. In a septic arthritis model, an isogenic S. aureus mutant is significantly less virulent than the Cna-expressing wild-type parental strain[27]. Also, introduction of the cna
Fibrinogen-binding MSCRAMMs
Until recently, it was thought that the ability of S. aureus to adhere to fibrinogen-containing substrates and to clump in the presence of fibrinogen resulted from the clumping factor ClfA (Ref. [35]). ClfA mediates bacterial attachment to plasma clots formed in vitro and to plastic biomaterial exposed to canine and human blood during short-term (<6 h) conditioning12, 13. Thus, it is probably a significant factor in wound and foreign body infection. In a rat endocarditis model, a ClfA− mutant is
The Sdr family of surface proteins
ClfA and ClfB are members of a larger family of structurally related surface proteins characterized by the presence of the R-domain containing the Ser–Asp dipeptide repeats[46]. When DNA encoding the R-domain of clfA was used as a probe in Southern blots of S. aureus genomic DNA, three HindIII fragments, in addition to that carrying clfA, reacted strongly[35]. Each of these loci has now been sequenced. One encodes ClfB (Ref. [37]), and the other two encode three closely linked genes called sdrC
Conclusions
Pathogenic bacteria often have an arsenal of secreted and surface-anchored proteins by which they interact with the host. S. aureus, which appears primarily to be an extracellular pathogen and is able to cause a multitude of persistent infections, is likely to use numerous host tissue adherence mechanisms and strategies to counter the host's defense systems. Through conventional cloning and sequencing approaches, we have begun to identify the repertoire of staphylococcal surface proteins. This
Questions for future research
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What are the functions of the Sdr proteins?
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What is the full repertoire of surface proteins from Staphylococcus aureus?
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What role do MSCRAMMS (microbial surface components recognizing adhesive matrix molecules) and other surface proteins play in colonization of the host?
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Can MSCRAMMS be used as vaccines?
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Why is the immune response to staphylococcal infection apparently insufficient to combat reinfection?
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How are extracellular ligand-binding activities of MSCRAMMS regulated?
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What are the roles of
Acknowledgements
We acknowledge past and present members of our laboratories, who have contributed to the development of our understanding of surface proteins of S. aureus, and Inhibitex Inc. for financial support. T.J.F. thanks The Wellcome Trust, The Health Research Board of Ireland and BioResearch Ireland for grants. M.H. acknowledges support from NIH grants AR-44415 and 4I-26624 and USDA grant 35204-5046.
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