title: Virulence potential of the staphylococcal adhesin CNA in experimental arthritis is determined by its affinity for collagen.
abstract: 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).
  
  
  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.
authors.affiliation: The Center for Extracellular Matrix Biology, Texas A and M University System Health Science Center, Institute of Biosciences and Technology, Houston, Texas 77030, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xu
authors.forename: Jorge M
authors.initials: JM
authors.lastname: Rivas
authors.forename: Eric L
authors.initials: EL
authors.lastname: Brown
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Liang
authors.forename: Magnus
authors.initials: M
authors.lastname: Höök
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001169:Arthritis, Experimental / Q000382:microbiology / Q000473:pathology*; D001170:Arthritis, Infectious / Q000382:microbiology / Q000473:pathology*; D003094:Collagen / Q000378:metabolism*; D005260:Female; D006801:Humans; D007596:Joints / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D013203:Staphylococcal Infections / Q000382:microbiology / Q000473:pathology*; D013211:Staphylococcus aureus / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D018829:Adhesins, Bacterial; C048165:adhesin, Staphylococcus aureus; D003094:Collagen