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Gene Review

clfA  -  truncated clumping factor

Staphylococcus aureus RF122

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Disease relevance of clfA

  • To circumvent this problem, S. aureus clumping factor A (clfA) and fibronectin-binding protein A (fnbA) genes were constitutively expressed in poorly pathogenic Lactococcus lactis using the recently described pOri23 vector [1].
  • Using genomic DNA from 25 unrelated strains and probes specific for each gene, we assessed the prevalence of the Staphylococcus aureus (Sa) adhesion genes cna, fnbA, fnbB, fib, clfA, fbpA, ebpS and map [2].
  • Also, ancrod treatment tended to enhance the arthritis induced by a clfA mutant strain (DU5876), indicating that fibrinogen depletion exacerbates septic arthritis in a ClfA-independent manner [3].

High impact information on clfA

  • The clfA gene encodes a fibrinogen-binding protein with an apparent molecular mass of c. 130 kDa [4].
  • In addition, the cloned clfA gene on a shuttle plasmid allowed the weakly clumping strain 8325-4 to form clumps with the same avidity as the wild-type strain Newman and also significantly enhanced the adherence of 8325-4 strains [4].
  • A single copy of the clfA gene, when introduced into the chromosome of the mutant strains, fully complemented the clumping deficiency of these strains and restored the ability of these mutants to adhere to fibrinogen-coated PMMA [4].
  • 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 [5].
  • Real-time quantitative reverse transcription-PCR demonstrated increased expression of clfA and fnb genes by the hemB mutant compared to its isogenic parent [6].

Biological context of clfA

  • As expected, the clfA mutant bound less soluble 125I-labeled fibrinogen than the corresponding coa mutant in agr+ strains; however, with agr mutant strains, the upregulation in fibrinogen binding capacity correlated mostly with the increased expression and transcription of coagulase as shown by Western (immunoblot) and Northern (RNA) blot analysis [7].
  • Furthermore, coagulase did not increase the pathogenicity of clfA-positive streptococci when both clfA and coa genes were simultaneously expressed in an artificial minioperon in streptococci [8].
  • 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 [9].
  • There was a strong association between RAPD type and the clfA region-R genotype among Irish isolates [10].
  • In the present study, the impact of ClfA expression on the phagocytosis of S. aureus by macrophages was investigated using clfA-positive and clfA-negative isogenic strains [11].

Anatomical context of clfA

  • In contrast to the in vitro results, quantities of clfA transcripts in the unattached bacteria of the exudates never exceeded the level of clfA transcripts in the sessile bacteria attached to glass beads [12].
  • Lactococci carrying pOri23-clfA produced an unaltered and functional 130-kDa ClfA protein attached to their cell walls [13].
  • On the other hand, a clfA mutant strain caused more release of proinflammatory mediators by macrophages than its clfA-positive parental strain [11].

Associations of clfA with chemical compounds

  • PVL(+) HA-MRSA and CA-MRSA shared the same multi-locus sequence type (ST30) and methicillin resistance cassette (SCCmecIV), but were divergent in oxacillin resistance, spa typing, PFGE analysis or clfA gene analysis [14].

Regulatory relationships of clfA

  • In contrast, clfA-expressing and fnbA-expressing lactococci required only 10(5) CFU to infect the majority of the animals (P < 0.00005) [1].

Other interactions of clfA

  • All investigated strains harbored the clfA, clfB, coa, spa, and nuc genes, but the presence of their products was not detected by the phenotypic methods [15].
  • Taken together, the present observations suggest that if antiadhesin therapy were to be developed, at least both of the clfA and fnbA products should be blocked for the therapy to be effective [1].
  • All 25 strains encoded fib, clfA, ebpS, map and at least one of the fnb genes. fbpA and coa appeared to be allelic variants of the same gene with the fbpA variant being present in only four of 25 isolates. cna was present in 10 of 25 strains [2].

Analytical, diagnostic and therapeutic context of clfA

  • DNA sequencing, Southern blotting, and PCR analysis indicate that PS12 contained two Tn551 insertions within the clumping factor A (ClfA) locus (clfA) [16].
  • To elucidate this question, we investigated clfA transcript levels in an animal model of device-related infection and in planktonic and sessile bacteria grown in vitro [12].


  1. Reassessing the role of Staphylococcus aureus clumping factor and fibronectin-binding protein by expression in Lactococcus lactis. Que, Y.A., François, P., Haefliger, J.A., Entenza, J.M., Vaudaux, P., Moreillon, P. Infect. Immun. (2001) [Pubmed]
  2. Prevalence and chromosomal map location of Staphylococcus aureus adhesin genes. Smeltzer, M.S., Gillaspy, A.F., Pratt, F.L., Thames, M.D., Iandolo, J.J. Gene (1997) [Pubmed]
  3. Clumping factor A-mediated virulence during Staphylococcus aureus infection is retained despite fibrinogen depletion. Palmqvist, N., Josefsson, E., Tarkowski, A. Microbes Infect. (2004) [Pubmed]
  4. Molecular characterization of the clumping factor (fibrinogen receptor) of Staphylococcus aureus. McDevitt, D., Francois, P., Vaudaux, P., Foster, T.J. Mol. Microbiol. (1994) [Pubmed]
  5. 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]
  6. Increased expression of clumping factor and fibronectin-binding proteins by hemB mutants of Staphylococcus aureus expressing small colony variant phenotypes. Vaudaux, P., Francois, P., Bisognano, C., Kelley, W.L., Lew, D.P., Schrenzel, J., Proctor, R.A., McNamara, P.J., Peters, G., Von Eiff, C. Infect. Immun. (2002) [Pubmed]
  7. Influence of agr on fibrinogen binding in Staphylococcus aureus Newman. Wolz, C., McDevitt, D., Foster, T.J., Cheung, A.L. Infect. Immun. (1996) [Pubmed]
  8. Study of Staphylococcus aureus pathogenic genes by transfer and expression in the less virulent organism Streptococcus gordonii. Stutzmann Meier, P., Entenza, J.M., Vaudaux, P., Francioli, P., Glauser, M.P., Moreillon, P. Infect. Immun. (2001) [Pubmed]
  9. 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]
  10. Molecular population and virulence factor analysis of Staphylococcus aureus from bovine intramammary infection. Fitzgerald, J.R., Hartigan, P.J., Meaney, W.J., Smyth, C.J. J. Appl. Microbiol. (2000) [Pubmed]
  11. Expression of staphylococcal clumping factor A impedes macrophage phagocytosis. Palmqvist, N., Patti, J.M., Tarkowski, A., Josefsson, E. Microbes Infect. (2004) [Pubmed]
  12. Transcription of clumping factor A in attached and unattached Staphylococcus aureus in vitro and during device-related infection. Wolz, C., Goerke, C., Landmann, R., Zimmerli, W., Fluckiger, U. Infect. Immun. (2002) [Pubmed]
  13. Expression of Staphylococcus aureus clumping factor A in Lactococcus lactis subsp. cremoris using a new shuttle vector. Que, Y.A., Haefliger, J.A., Francioli, P., Moreillon, P. Infect. Immun. (2000) [Pubmed]
  14. Molecular nature of methicillin-resistant Staphylococcus aureus derived from explosive nosocomial outbreaks of the 1980s in Japan. Taneike, I., Otsuka, T., Dohmae, S., Saito, K., Ozaki, K., Takano, M., Higuchi, W., Takano, T., Yamamoto, T. FEBS Lett. (2006) [Pubmed]
  15. Characteristics of Staphylococcus aureus Strains Isolated in Poland in 1996 to 2004 That Were Deficient in Species-Specific Proteins. Luczak-Kadlubowska, A., Krzyszton-Russjan, J., Hryniewicz, W. J. Clin. Microbiol. (2006) [Pubmed]
  16. Clumping factor A mediates binding of Staphylococcus aureus to human platelets. Siboo, I.R., Cheung, A.L., Bayer, A.S., Sullam, P.M. Infect. Immun. (2001) [Pubmed]
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