No abstract

Staphylococcus aureus is a versatile and harmful human pathogen in both hospital- and community-acquired infections. S. aureus can initiate host infection by adhering to components of the extracellular matrix. Adherence is mediated by a variety of protein adhesins of the microbial surface component recognizing adhesive matrix molecule (MSCRAMM) family. In this article, we describe these MSCRAMMs in terms of structural organization and ligand-binding capacity and discuss their role as a possible target for immunotherapy.

Staphylococcus growth on medical devices represents a common occurrence that can lead to serious illness and death. Biomaterial-associated infection, mostly caused by Staphylococcus epidermidis and Staphylococcus aureus, is fairly complicated by the organism' development of a biofilm, which provides a microenvironment that protects from attack by the host immune system and antibiotics. In this review we present recent insights regarding S. aureus and S. epidermidis structural and functional factors that are effective in biofilm development and describe the regulation of their expression. On the basis of the knowledge gained, we also present the potential and limits of current biochemical and biophysical strategies aimed at preventing biofilm formation or at the treatment of established mature biofilms.

Fibronectin-binding proteins A and B are multifunctional LPXTG staphylococcal adhesins, comprising an N-terminal region that binds fibrinogen and elastin, and a C-terminal domain that interacts with fibronectin. The C-terminal domain of fibronectin-binding protein A is organized into 11 tandem repeats, six of which bind the ligand with high affinity; other sites bind more weakly. Fibronectin-binding protein B has been postulated to harbor 10 rather than 11 repeats, but it contains the same number of highaffinity fibronectin-binding sites as fibronectin-binding protein A. In this study, we confirm this prediction and show that six of 10 sites bind with dissociation constants in the nanomolar range. We also found that the fulllength repetitive region of fibronectin-binding protein B stimulated the production of a mAb (15E11) that binds with high affinity to an epitope shared by repeats 9 and 10 from both adhesins. With the use of truncated fragments of repeat 9 of fibronectin-binding protein A, we mapped the antibody epitope to the N-terminal segment and the fibronectin-binding site to the C-terminal segment of the repeat. The distinct localization of the 15E11 epitope and the fibronectin-binding site suggests that the interfering effect of the antibody might result from steric hindrance or a conformational change in the structure that reduces the accessibility of fibronectin to its binding determinant. The epitope is well exposed on the surface of staphylococcal cells, as determined by genetic analyses, fluorescence microscopy, and flow cytometry. When incubated with cells of Staphylococcs aureus strains, 15E11 inhibits attachment of bacteria to surface-coated fibronectin by almost 70%.