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.


RESULTS
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.
Wertheim
Heiman F L
HF
Erasmus MC, University Medical Center Rotterdam, Department of Medical Microbiology and Infectious Diseases, Rotterdam, The Netherlands. h.wertheim@erasmusmc.nl
Walsh
Evelyn
E
Choudhurry
Roos
R
Melles
Damian C
DC
Boelens
Hélène A M
HA
Miajlovic
Helen
H
Verbrugh
Henri A
HA
Foster
Timothy
T
van Belkum
Alex
A
D000281:Administration, Intranasal; D000328:Adult; D001422:Bacterial Adhesion; D002353:Carrier State / Q000382:microbiology*; D003030:Coagulase / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D003470:Culture Media / Q000494:pharmacology; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D006801:Humans; D053550:Keratin-10 / Q000235:genetics / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009296:Nasal Cavity / Q000382:microbiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D013203:Staphylococcal Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity*
D003030:Coagulase; D003470:Culture Media; D011993:Recombinant Fusion Proteins; D053550:Keratin-10