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Key role for clumping factor B in Staphylococcus aureus nasal colonization of humans.

Wertheim HF, Walsh E, Choudhurry R, Melles DC, Boelens HA, Miajlovic H, Verbrugh HA, Foster T, van Belkum A - PLoS Med. (2008)

Bottom Line: 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 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.

View Article: PubMed Central - PubMed

Affiliation: Erasmus MC, University Medical Center Rotterdam, Department of Medical Microbiology and Infectious Diseases, Rotterdam, The Netherlands. h.wertheim@erasmusmc.nl

ABSTRACT

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.

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Study DesignFirst, the left or right nostril was randomized to receive the inoculation mix, containing strains 8325-4 (WT) and DU5997 (mutant strain). Second, the contralateral nostril was randomized to receive either the naturally occurring (“WT” in figure) or mutant strain.
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pmed-0050017-g001: Study DesignFirst, the left or right nostril was randomized to receive the inoculation mix, containing strains 8325-4 (WT) and DU5997 (mutant strain). Second, the contralateral nostril was randomized to receive either the naturally occurring (“WT” in figure) or mutant strain.

Mentions: From all enrolled volunteers, we obtained two nasal cultures 1 wk apart before artificial inoculation in order to differentiate between persistent, intermittent, and non-carriers, as described previously (Nouwen et al. [26]). To be classified as a persistent carrier, both nasal cultures needed to be positive with a S. aureus.. In case of one positive culture, the volunteer was classified as an intermittent carrier. For non-carriers, all cultures needed to be negative. Figure 1 illustrates the design of the study. Decolonization treatment was started for all volunteers (nasal mupirocin twice daily for 5 d in combination with once-daily washing with chlorhexidine-containing soap for 5 d [Hibiscrub; Regent Medical]). Five weeks after mupirocin and chlorhexidine treatment, nostrils were cultured again to assess colonization status, and experimental nasal inoculation was performed.


Key role for clumping factor B in Staphylococcus aureus nasal colonization of humans.

Wertheim HF, Walsh E, Choudhurry R, Melles DC, Boelens HA, Miajlovic H, Verbrugh HA, Foster T, van Belkum A - PLoS Med. (2008)

Study DesignFirst, the left or right nostril was randomized to receive the inoculation mix, containing strains 8325-4 (WT) and DU5997 (mutant strain). Second, the contralateral nostril was randomized to receive either the naturally occurring (“WT” in figure) or mutant strain.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2194749&req=5

pmed-0050017-g001: Study DesignFirst, the left or right nostril was randomized to receive the inoculation mix, containing strains 8325-4 (WT) and DU5997 (mutant strain). Second, the contralateral nostril was randomized to receive either the naturally occurring (“WT” in figure) or mutant strain.
Mentions: From all enrolled volunteers, we obtained two nasal cultures 1 wk apart before artificial inoculation in order to differentiate between persistent, intermittent, and non-carriers, as described previously (Nouwen et al. [26]). To be classified as a persistent carrier, both nasal cultures needed to be positive with a S. aureus.. In case of one positive culture, the volunteer was classified as an intermittent carrier. For non-carriers, all cultures needed to be negative. Figure 1 illustrates the design of the study. Decolonization treatment was started for all volunteers (nasal mupirocin twice daily for 5 d in combination with once-daily washing with chlorhexidine-containing soap for 5 d [Hibiscrub; Regent Medical]). Five weeks after mupirocin and chlorhexidine treatment, nostrils were cultured again to assess colonization status, and experimental nasal inoculation was performed.

Bottom Line: 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 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.

View Article: PubMed Central - PubMed

Affiliation: Erasmus MC, University Medical Center Rotterdam, Department of Medical Microbiology and Infectious Diseases, Rotterdam, The Netherlands. h.wertheim@erasmusmc.nl

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus