Key role for clumping factor B in Staphylococcus aureus nasal colonization of humans
BACKGROUND: Staphylococcus aureus permanently colonizes the vestibulum nasi of one-fifth of the human population, which is a risk factor for autoinfection. The precise mechanisms whereby S. aureus colonizes the nose are still unknown. The staphylococcal cell-wall protein clumping factor B (ClfB) promotes adhesion to squamous epithelial cells in vitro and might be a physiologically relevant colonization factor. METHODS AND FINDINGS: We define the role of the staphylococcal cytokeratin-binding protein ClfB in the colonization process by artificial inoculation of human volunteers with a wild-type strain and its single locus ClfB knock-out mutant. The wild-type strain adhered to immobilized recombinant human cytokeratin 10 (CK10) in a dose-dependent manner, whereas the ClfB(-) mutant did not. The wild-type strain, when grown to the stationary phase in a poor growth medium, adhered better to CK10, than when the same strain was grown in a nutrient-rich environment. Nasal cultures show that the mutant strain is eliminated from the nares significantly faster than the wild-type strain, with a median of 3 +/- 1 d versus 7 +/- 4 d (p = 0.006). Furthermore, the wild-type strain was still present in the nares of 3/16 volunteers at the end of follow-up, and the mutant strain was not. CONCLUSIONS: The human colonization model, in combination with in vitro data, shows that the ClfB protein is a major determinant of nasal-persistent S. aureus carriage and is a candidate target molecule for decolonization strategies.
|Keywords||Administration, Intranasal, Adult, Bacterial Adhesion, Carrier State/*microbiology, Coagulase/biosynthesis/deficiency/genetics/*physiology, Culture Media/pharmacology, Double-Blind Method, Enzyme-Linked Immunosorbent Assay, Female, Gene Expression Regulation, Bacterial/drug effects, Humans, Keratin-10/genetics/physiology, Male, Middle Aged, Nasal Cavity/*microbiology, Recombinant Fusion Proteins/physiology, Staphylococcal Infections/*microbiology, Staphylococcus aureus/drug effects/genetics/*pathogenicity|
|Persistent URL||dx.doi.org/10.1371/journal.pmed.0050017, hdl.handle.net/1765/17735|
Wertheim, H.F.L., Walsh, E.J., Choudhurry, R.S.R., Melles, D.C., Boelens, H.A.M., Miajlovic, H., … van Belkum, A.F.. (2008). Key role for clumping factor B in Staphylococcus aureus nasal colonization of humans. PLoS Medicine, 5(1), 104–112. doi:10.1371/journal.pmed.0050017