L. Visai et al., Monoclonal antibodies to CNA, a collagen-binding microbial surface component recognizing adhesive matrix molecules, detach Staphylococcus aureus froma collagen substrate, J BIOL CHEM, 275(51), 2000, pp. 39837-39845
Previous studies showed that Staphylococcus aureus expresses a collagen-bin
ding MSCRAMM (Microbial Surface Component Recognizing Adhesive Matrix Molec
ules), CNA, that is necessary and sufficient for S. aureus cells to adhere
to cartilage and is a virulence factor in experimental septic arthritis. We
have now used a monoclonal antibody (mAb) approach to further analyze the
structure and function of CNA. 22 mAbs raised against the minimal ligand bi
nding domain, CNA-(151-318), were shown to bind to the MSCRAMM with similar
affinity. All mAbs appear to recognize conformation-dependent epitopes tha
t were mapped throughout the CNA-(151-318) domain using a chimeric strategy
where segments of CNA are grafted on ACE, a structurally related MSCRAMM f
rom Enterococcus faecalis. These mAbs were able to inhibit I-125-collagen b
inding to CNA(151-318) as well as to intact S. aureus cells. They also inte
rfered with the attachment of bacteria to collagen substrates. Furthermore,
some of the mAbs could effectively displace I-125-collagen bound to the ba
cteria. These displacing mAbs were also able to detach bacteria that had ad
hered to a collagen substrate in a preincubation, raising the possibility t
hat some of the mAbs may be used as therapeutic agents.