MSCRAMM--targeted vaccines and immunotherapy for staphylococcal infection.

Hospital-acquired infections are associated with prolonged hospitalization and an increase in both healthcare costs and resources. Advances in sophisticated medical procedures, an increase in the number of immunocompromised patients, and the continued emergence of resistance to conventional antibiotic therapy has created a need for alternative strategies to prevent and treat infectious bacterial diseases. Immunoprevention and immunotherapy targeting microbial surface components recognizing adhesive matrix molecule (MSCRAMM) proteins are viable approaches to potentially impede bacterial adherence, eliminate colonization, and minimize hematogenous dissemination, thereby halting the inception and progression of infection. This review summarizes several investigative efforts where staphylococcal MSCRAMM proteins are being utilized in the design of subunit vaccines and in the development of innovative therapeutic strategies that could be implemented following the onset of infection to manage severe and life-threatening disease.

Virulence potential of the staphylococcal adhesin CNA in experimental arthritis is determined by its affinity for collagen.

BACKGROUND: Staphylococcus aureus is a major cause of bacterial arthritis, which often results in severe joint damage. CNA, a collagen adhesin of S. aureus, was shown to be a virulence factor in several animal models. However, the precise molecular mechanism by which CNA contributes to virulence remains unclear. METHODS: We examined the role of the collagen-binding function of CNA in a mouse model of septic arthritis by comparing the virulence of isogenic strains of S. aureus expressing (1) wild-type CNA, (2) a truncated form of CNA (CNA35) with a higher affinity for collagen than the wild type, (3) CNA35 containing a single point mutation resulting in loss of collagen binding, (4) CNA lacking the collagen-binding domain, and (5) the collagen-binding domain of ACE (adhesin of collagen from Enterococcus faecalis). RESULTS AND CONCLUSIONS: The results provide, for the first time, direct evidence that the virulence of CNA depends on its collagen-binding ability. Collagen binding facilitated early colonization of the joints of mice. Furthermore, the virulence potential of the adhesin is determined by the adhesin's affinity for its ligand, as well as its binding kinetics.