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.
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.
Heiman Wertheim and colleagues investigate the role ofStaphylococcus aureus clumping factor B, a cell wall protein, in bacterial adherence to epithelial cells and persistent colonization of human nostrils.
Staphylococcus aureus are common bacteria that normally live on the skin. They also colonize the nostrils of about one in five adults permanently and another one in three adults intermittently. Although these bacteria usually coexist peacefully with their human carriers, they can cause minor infections such as pimples and boils if they enter the skin through a cut or a sore. They can also cause potentially life-threatening infections such as blood poisoning and pneumonia. These serious, invasive infections are often “autoinfections.” That is, they are caused by strains of S. aureus that are present in the patient's nose before they become ill. Minor S. aureus infections can be treated without antibiotics—by draining a boil, for example. Invasive infections are usually treated with antibiotics such as flucloxacillin.
Why Was This Study Done?
There is no effective vaccine against S. aureus infections and these bacteria are becoming increasingly resistant to flucloxacillin, methicillin, and other antibiotics. Worryingly, although methicillin-resistant S. aureus (MRSA) infections occur most frequently among people in health-care facilities who have weakened immune systems, community-acquired MRSA infections among otherwise healthy people are increasingly common. Consequently, new ways to avoid S. aureus infections are urgently needed. Because persistent nasal carriers of S. aureus have an increased risk of infection, one strategy might be to prevent nasal colonization with S. aureus. How these bacteria colonize the nose is poorly understood, but is likely to involve interactions between molecules expressed on the surface of the bacteria and molecules expressed on the surface of the cells lining the nostrils. In this study, the researchers use a new human nasal colonization assay to investigate the involvement of a bacterial surface protein called clumping factor B (ClfB) in the survival of S. aureus in the human nose. ClfB binds to cytokeratin 10, a protein expressed by cells lining the human nose, and has been implicated in the colonization of mouse noses by S. aureus.
What Did the Researchers Do and Find?
The researchers introduced a strain of S. aureus that made ClfB and an otherwise identical, mutant strain that lacked ClfB into the nostrils of healthy human volunteers and measured how long the two strains survived. For safety reasons, the S. aureus strains used in this study have an additional defect that makes them less likely to colonize and persist in the human nose than the strains found in natural S. aureus carriers. Although both strains grew equally well in the laboratory, the mutant strain was eliminated from human noses much quicker than the strain that made ClfB. Mutant bacteria lacking ClfB were cleared from the nostrils of all the volunteers within two weeks, whereas the bacteria that made ClfB were still present in some of the volunteers four weeks after their introduction. When the researchers investigated how well the two strains stuck to a layer of human cytokeratin 10 in a plastic dish, they found that the bacteria that made ClfB stuck to the human protein but the mutant bacteria did not. Furthermore, the strain with ClfB stuck particularly well to cytokeratin 10 when the bacteria had been grown in conditions where nutrients were limiting, a situation that mimics bacterial growth in the human nose.
What Do These Findings Mean?
These findings show that ClfB is an important factor in the establishment of human nasal colonization by S. aureus and suggest that ClfB might be a target for S. aureus decolonization strategies. Furthermore, although ClfB is clearly important in human nasal colonization by S. aureus, it is likely that additional bacterial factors will also be involved in this process. The human nasal colonization model used in this study may be useful in the identification of these additional factors and also as a test bed for potential S. aureus decolonization strategies.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050017.
The MedlinePlus encyclopedia has a page on Staphylococcus aureus and MRSA (in English and Spanish)
The US Centers for Disease Control and Prevention provides information on community-associated MRSA (in English and Spanish)
The UK National Health Service's health website (NHS Direct) provides information about staphylococcal infections and about MRSA
The UK Health Protection Agency provides information about Staphylococcus aureus