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clfB  -  clumping factor B

Staphylococcus aureus RF122

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Disease relevance of clfB

  • Double-Locus Sequence Typing Using clfB and spa, a Fast and Simple Method for Epidemiological Typing of Methicillin-Resistant Staphylococcus aureus [1].
  • Although clfB could affect endovascular infection, its importance in experimental endocarditis was limited [2].
  • By expressing a range of S. aureus adhesins on the surface of the heterologous host Lactococcus lactis, we demonstrated that adherence to epidermal cytokeratins was conferred by ClfB [3].
  • The mouse immunization studies demonstrate that ClfB is an attractive component for inclusion in a vaccine to reduce S. aureus nasal colonization in humans, which in turn may diminish the risk of staphylococcal infection [4].

High impact information on clfB

  • Antibodies raised against the central N2 domain of the A-region were the most effective at inhibiting bacterial adhesion to immobilized fibrinogen, although anti-N3 or anti-N1 antibodies also caused some reduction in ClfB-mediated adherence to fibrinogen [5].
  • The loss of ClfB protein from cells in stationary phase was due to expression ending before cells stopped growing, combined with shedding of some of the protein into the growth medium and dilution of those molecules remaining on the cell surface during the two to three cell division events leading to stationary phase [6].
  • Analysis of proteins released from the cell wall of S. aureus Newman by Western immunoblotting using antibody raised against the recombinant A region of ClfB identified a 124 kDa protein as the clfB gene product [7].
  • ClfB-dependent bacterial adherence to immobilized fibrinogen was inhibited by millimolar concentrations of Ca2+ and Mn2+, which indicates that, like ClfA, ligand binding by ClfB is regulated by a low-affinity inhibitory cation binding site [7].
  • In contrast, mutants deficient in sortase A or clumping factor B (ClfB) showed reduced nasal colonization [4].

Chemical compound and disease context of clfB


Biological context of clfB

  • We showed that by using only 3' partial sequences of approximately 500 bp, the majority of each marker's discriminatory power was displayed, and using the partial sequences, the best performance was obtained with the combination of clfB and spa (57 genotypes; index of discrimination of 0.94) [1].
  • In contrast, clfB complementation on a multicopy plasmid significantly increased infectivity (P<0.05) over the deleted mutants [2].
  • The target regions of strains representative of epidemic clones and genetically related methicillin-susceptible S. aureus isolates from the 1960s that were sequenced included the R domains of clfA and clfB; the D, W, and M regions of fnbA and fnbB; and three regions in the agr operon [9].
  • To overcome this constraint, we developed a typing system using DNA sequence analysis of the serine-aspartate (SD) repeat-encoding region within the gene encoding the keratin- and fibrinogen-binding clumping factor B (clfB typing) and tested whether it is capable of discriminating within clonal groups [10].
  • Five staphylococcal VNTR loci (sdr, clfA, clfB, ssp, and spa) were subjected to analysis, and it was shown that the method allows typing of S. aureus strains with the discriminatory power and reproducibility of pulsed-field gel electrophoresis while at the same time being rapid and applicable to analysis of large numbers of isolates [11].

Anatomical context of clfB

  • ClfB also promoted adherence of L. lactis cells to a human keratinocyte cell line [3].
  • Expression of ClfB promoted adherence of L. lactis to human desquamated nasal epithelial cells, and a mutant of S. aureus defective in ClfB had reduced adherence compared with wild type [3].

Other interactions of clfB

  • By using three sets of 48 MRSA strains comprising isolates that were (i) genetically highly diverse, (ii) genetically related, and (iii) obtained from long-term carriers, we analyzed the performance of the four highly polymorphic S. aureus markers: clfA, clfB, fnbA, and spa [1].

Analytical, diagnostic and therapeutic context of clfB


  1. Double-Locus Sequence Typing Using clfB and spa, a Fast and Simple Method for Epidemiological Typing of Methicillin-Resistant Staphylococcus aureus. Kuhn, G., Francioli, P., Blanc, D.S. J. Clin. Microbiol. (2007) [Pubmed]
  2. Contribution of clumping factor B to pathogenesis of experimental endocarditis due to Staphylococcus aureus. Entenza, J.M., Foster, T.J., Ni Eidhin, D., Vaudaux, P., Francioli, P., Moreillon, P. Infect. Immun. (2000) [Pubmed]
  3. Staphylococcus aureus clumping factor B (ClfB) promotes adherence to human type I cytokeratin 10: implications for nasal colonization. O'Brien, L.M., Walsh, E.J., Massey, R.C., Peacock, S.J., Foster, T.J. Cell. Microbiol. (2002) [Pubmed]
  4. Immunization with Staphylococcus aureus clumping factor B, a major determinant in nasal carriage, reduces nasal colonization in a murine model. Schaffer, A.C., Solinga, R.M., Cocchiaro, J., Portoles, M., Kiser, K.B., Risley, A., Randall, S.M., Valtulina, V., Speziale, P., Walsh, E., Foster, T., Lee, J.C. Infect. Immun. (2006) [Pubmed]
  5. Structural organization of the fibrinogen-binding region of the clumping factor B MSCRAMM of Staphylococcus aureus. Perkins, S., Walsh, E.J., Deivanayagam, C.C., Narayana, S.V., Foster, T.J., Höök, M. J. Biol. Chem. (2001) [Pubmed]
  6. Loss of clumping factor B fibrinogen binding activity by Staphylococcus aureus involves cessation of transcription, shedding and cleavage by metalloprotease. McAleese, F.M., Walsh, E.J., Sieprawska, M., Potempa, J., Foster, T.J. J. Biol. Chem. (2001) [Pubmed]
  7. Clumping factor B (ClfB), a new surface-located fibrinogen-binding adhesin of Staphylococcus aureus. Ní Eidhin, D., Perkins, S., Francois, P., Vaudaux, P., Höök, M., Foster, T.J. Mol. Microbiol. (1998) [Pubmed]
  8. DNA sequence-based tandem repeat analysis of the clfB gene is less discriminatory than spa typing for methicillin-resistant Staphylococcus aureus. Harmsen, D., Claus, H., Vogel, U. Int. J. Med. Microbiol. (2005) [Pubmed]
  9. Analysis of the genetic variability of virulence-related loci in epidemic clones of methicillin-resistant Staphylococcus aureus. Gomes, A.R., Vinga, S., Zavolan, M., de Lencastre, H. Antimicrob. Agents Chemother. (2005) [Pubmed]
  10. Comparative sequencing of the serine-aspartate repeat-encoding region of the clumping factor B gene (clfB) for resolution within clonal groups of Staphylococcus aureus. Koreen, L., Ramaswamy, S.V., Naidich, S., Koreen, I.V., Graff, G.R., Graviss, E.A., Kreiswirth, B.N. J. Clin. Microbiol. (2005) [Pubmed]
  11. New method for typing Staphylococcus aureus strains: multiple-locus variable-number tandem repeat analysis of polymorphism and genetic relationships of clinical isolates. Sabat, A., Krzyszton-Russjan, J., Strzalka, W., Filipek, R., Kosowska, K., Hryniewicz, W., Travis, J., Potempa, J. J. Clin. Microbiol. (2003) [Pubmed]
  12. Characterization of 26 isolates of Staphylococcus aureus, predominantly from dairy sheep, using four different techniques of molecular epidemiology. Vautor, E., Jay, C., Chevalier, N., Visomblin, N., Vernet, G., Pépin, M. J. Vet. Diagn. Invest. (2005) [Pubmed]
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