Date Published: January 15, 2008
Publisher: Public Library of Science
Author(s): Heiman F. L Wertheim, Evelyn Walsh, Roos Choudhurry, Damian C Melles, Hélène A. M Boelens, Helen Miajlovic, Henri A Verbrugh, Timothy Foster, Alex van Belkum, Henry Chambers
Abstract: BackgroundStaphylococcus 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 FindingsWe 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.ConclusionsThe 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.
Partial Text: Staphylococcus aureus remains one of the prime human bacterial pathogens, associated with significant morbidity and mortality worldwide. The combination of an increasing number of antimicrobials to which this pathogen has become resistant and the lack of an effective vaccine underscores that alternatives to combating S. aureus disease are urgently required. In addition, community-acquired infections with methicillin-resistant S. aureus (MRSA) are rising steeply [1,2]. Approximately 80% of invasive S. aureus infections are autologous [3,4] in that they are caused by strains carried in the nose by the patient prior to illness. Approximately 20% of the adult population carries S. aureus in their nose persistently, another 30% intermittently, whereas 50% are non-carriers .
We report here the first study, to our knowledge, of healthy human volunteers being coinoculated with an S. aureus 8325–4 strain and an isogenic mutant defective in the MSCRAMM ClfB (DU5997). We show that ClfB is an important factor for establishing human nasal colonization by S. aureus, as the ClfB− mutant (DU5997) was not able to survive in the human nose after 2 wk. In contrast, the 8325–4 strain was still present at the end of follow-up in three volunteers.