1887

Abstract

EDIN-B (epidermal cell differentiation inhibitor-B; also termed C3Stau) is an exotoxin of which ADP-ribosylates and inactivates Rho GTP binding proteins. The EDIN-B gene () and the gene for exfoliative toxin D () make up the central part of a recently described pathogenicity island. Here we evaluated the prevalence and genetic organization of the pathogenicity island in invasive isolates, and characterized transcription and EDIN-B production using artificial constructs transduced in strains RN6390 and Newman. We found that eight out of 121 (7 %) blood culture isolates harbour , which is organized in three novel variants of the original pathogenicity island. In the serum of patients infected with -positive , significant titres of anti-EDIN-B antibodies could be detected. Regulation of transcription depended on the but not on the regulatory system. Furthermore, retrieval of EDIN-B protein secreted by RN6390 required the presence of 2-macroglobulin to inhibit the activity of extracellular proteases. These data suggest that the EDIN-B toxin is produced during human infection, is part of a highly variable pathogenicity island and can be controlled by the gene regulon and secreted bacterial proteases.

Keyword(s): CC, clonal complex
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2010-03-01
2020-01-24
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References

  1. Aepfelbacher, M., Essler, M., Huber, E., Sugai, M. & Weber,P. C. ( 1997; ). Bacterial toxins block endothelial woundrepair. Evidence that Rho GTPases control cytoskeletal rearrangements in migratingendothelial cells. Arterioscler Thromb Vasc Biol 17, 1623–1629.[CrossRef]
    [Google Scholar]
  2. Aepfelbacher, M., Trasak, C. & Ruckdeschel, K. ( 2007; ). Effector functions of pathogenic Yersinia species. Thromb Haemost 98, 521–529.
    [Google Scholar]
  3. Aktories, K. & Barbieri, J. T. ( 2005; ). Bacterial cytotoxins: targeting eukaryotic switches. Nat RevMicrobiol 3, 397–410.
    [Google Scholar]
  4. Arvidson, S. & Tegmark, K. ( 2001; ).Regulation of virulence determinants in Staphylococcus aureus. Int J Med Microbiol 291, 159–170.[CrossRef]
    [Google Scholar]
  5. Augustin, J. & Gotz, F. ( 1990; ).Transformation of Staphylococcus epidermidis and other staphylococcalspecies with plasmid DNA by electroporation. FEMS Microbiol Lett 54, 203–207.
    [Google Scholar]
  6. Ben Nejma, M., Mastouri, M., Bel Hadj Jrad, B. & Nour, M. ( 2008; ). Characterization of ST80 Panton–Valentineleukocidin-positive community-acquired methicillin-resistant Staphylococcusaureus clone in Tunisia. Diagn Microbiol Infect Disin press
    [Google Scholar]
  7. Bischoff, M., Dunman, P., Kormanec, J., Macapagal, D., Murphy,E., Mounts, W., Berger-Bachi, B. & Projan, S. ( 2004; ). Microarray-based analysis of the Staphylococcus aureus σ B regulon. J Bacteriol 186, 4085–4099.[CrossRef]
    [Google Scholar]
  8. Blevins, J. S., Beenken, K. E., Elasri, M. O., Hurlburt, B.K. & Smeltzer, M. S. ( 2002; ). Strain-dependentdifferences in the regulatory roles of sarA and agr in Staphylococcus aureus. Infect Immun 70, 470–480.[CrossRef]
    [Google Scholar]
  9. Bokoch, G. M. ( 2005; ). Regulation ofinnate immunity by Rho GTPases. Trends Cell Biol 15, 163–171.[CrossRef]
    [Google Scholar]
  10. Boyer, L., Doye, A., Rolando, M., Flatau, G., Munro, P., Gounon,P., Clément, R., Pulcini, C., Popoff, M. R. & other authors ( 2006; ). Induction of transient macroapertures in endothelialcells through RhoA inhibition by Staphylococcus aureus factors. J Cell Biol 173, 809–819.[CrossRef]
    [Google Scholar]
  11. Bronner, S., Monteil, H. & Prevost, G. ( 2004; ). Regulation of virulence determinants in Staphylococcus aureus: complexity and applications. FEMS Microbiol Rev 28, 183–200.[CrossRef]
    [Google Scholar]
  12. Bruckner, R. ( 1992; ). A series of shuttlevectors for Bacillus subtilis and Escherichia coli. Gene 122, 187–192.[CrossRef]
    [Google Scholar]
  13. Cassat, J., Dunman, P. M., Murphy, E., Projan, S. J., Beenken,K. E., Palm, K. J., Yang, S. J., Rice, K. C., Bayles, K. W. & Smeltzer,M. S. ( 2006; ). Transcriptional profiling of a Staphylococcus aureus clinical isolate and its isogenic agrand sarA mutants reveals global differences in comparison to thelaboratory strain RN6390. Microbiology 152, 3075–3090.[CrossRef]
    [Google Scholar]
  14. Chan, P. F. & Foster, S. J. ( 1998; ). Role of SarA in virulence determinant production and environmental signaltransduction in Staphylococcus aureus. J Bacteriol 180, 6232–6241.
    [Google Scholar]
  15. Cheung, A. L., Eberhardt, K. & Heinrichs, J. H. ( 1997; ). Regulation of protein A synthesis by the sar and agr loci of Staphylococcus aureus. Infect Immun 65, 2243–2249.
    [Google Scholar]
  16. Cheung, A. L., Bayer, A. S., Zhang, G., Gresham, H. & Xiong,Y. Q. ( 2004; ). Regulation of virulence determinants in vitro and in vivo in Staphylococcus aureus. FEMS Immunol Med Microbiol 40, 1–9.[CrossRef]
    [Google Scholar]
  17. Cheung, A. L., Nishina, K. A., Trotonda, M. P. & Tamber,S. ( 2008; ). The SarA protein family of Staphylococcusaureus. Int J Biochem Cell Biol 40, 355–361.[CrossRef]
    [Google Scholar]
  18. Chien, Y., Manna, A. C., Projan, S. J. & Cheung, A. L. ( 1999; ). SarA, a global regulator of virulence determinantsin Staphylococcus aureus, binds to a conserved motif essential for sar-dependent gene regulation. J Biol Chem 274, 37169–37176.[CrossRef]
    [Google Scholar]
  19. Chongtrakool, P., Ito, T., Ma, X. X., Kondo, Y., Trakulsomboon,S., Tiensasitorn, C., Jamklang, M., Chavalit, T., Song, J. H. & Hiramatsu,K. ( 2006; ). Staphylococcal cassette chromosome mec (SCCmec) typing of methicillin-resistant Staphylococcus aureus strains isolated in 11 Asian countries: a proposalfor a new nomenclature for SCCmec elements. AntimicrobAgents Chemother 50, 1001–1012.
    [Google Scholar]
  20. Clarke, S. R., Brummell, K. J., Horsburgh, M. J., McDowell,P. W., Mohamad, S. A., Stapleton, M. R., Acevedo, J., Read, R. C., Day, N.P. & other authors ( 2006; ). Identification of invivo-expressed antigens of Staphylococcus aureus and their use invaccinations for protection against nasal carriage. J Infect Dis 193, 1098–1108.[CrossRef]
    [Google Scholar]
  21. Czech, A., Yamaguchi, T., Bader, L., Linder, S., Kaminski, K.,Sugai, M. & Aepfelbacher, M. ( 2001; ). Prevalenceof Rho-inactivating epidermal cell differentiation inhibitor toxins in clinical Staphylococcus aureus isolates. J Infect Dis 184, 785–788.[CrossRef]
    [Google Scholar]
  22. Deurenberg, R. H. & Stobberingh, E. E. ( 2008; ). The evolution of Staphylococcus aureus. Infect Genet Evol 8, 747–763.[CrossRef]
    [Google Scholar]
  23. Deurenberg, R. H., Vink, C., Kalenic, S., Friedrich, A. W.,Bruggeman, C. A. & Stobberingh, E. E. ( 2007; ).The molecular evolution of methicillin-resistant Staphylococcus aureus. Clin Microbiol Infect 13, 222–235.[CrossRef]
    [Google Scholar]
  24. Dunman, P. M., Murphy, E., Haney, S., Palacios, D., Tucker-Kellogg,G., Wu, S., Brown, E. L., Zagursky, R. J., Shlaes, D. & Projan, S. J. ( 2001; ). Transcription profiling-based identificationof Staphylococcus aureus genes regulated by the agr and/or sarA loci. J Bacteriol 183, 7341–7353.[CrossRef]
    [Google Scholar]
  25. Duthie, E. S. & Lorenz, L. L. ( 1952; ). Staphylococcal coagulase; mode of action and antigenicity. J Gen Microbiol 6, 95–107.[CrossRef]
    [Google Scholar]
  26. Fitzgerald, J. R., Reid, S. D., Ruotsalainen, E., Tripp, T.J., Liu, M., Cole, R., Kuusela, P., Schlievert, P. M., Järvinen, A. &Musser, J. M. ( 2003; ). Genome diversification in Staphylococcus aureus: molecular evolution of a highly variable chromosomalregion encoding the staphylococcal exotoxin-like family of proteins. Infect Immun 71, 2827–2838.[CrossRef]
    [Google Scholar]
  27. Genth, H., Dreger, S. C., Huelsenbeck, J. & Just, I. ( 2008; ). Clostridium difficile toxins: more thanmere inhibitors of Rho proteins. Int J Biochem Cell Biol 40, 592–597.[CrossRef]
    [Google Scholar]
  28. Giachino, P., Engelmann, S. & Bischoff, M. ( 2001; ). σ B activity depends on RsbU in Staphylococcus aureus. J Bacteriol 183, 1843–1852.[CrossRef]
    [Google Scholar]
  29. Goerke, C. & Wolz, C. ( 2004; ). Regulatoryand genomic plasticity of Staphylococcus aureus during persistentcolonization and infection. Int J Med Microbiol 294, 195–202.[CrossRef]
    [Google Scholar]
  30. Goerke, C., Fluckiger, U., Steinhuber, A., Zimmerli, W. &Wolz, C. ( 2001; ). Impact of the regulatory loci agr, sarA and sae of Staphylococcus aureuson the induction of α-toxin during device-related infection resolvedby direct quantitative transcript analysis. Mol Microbiol 40, 1439–1447.[CrossRef]
    [Google Scholar]
  31. Gordon, J. J., Towsey, M. W., Hogan, J. M., Mathews, S. A. &Timms, P. ( 2006; ). Improved prediction of bacterialtranscription start sites. Bioinformatics 22, 142–148.[CrossRef]
    [Google Scholar]
  32. Hacker, J. & Kaper, J. B. ( 2000; ).Pathogenicity islands and the evolution of microbes. Annu Rev Microbiol 54, 641–679.[CrossRef]
    [Google Scholar]
  33. Harmsen, D., Claus, H., Witte, W., Rothganger, J., Turnwald,D. & Vogel, U. ( 2003; ). Typing of methicillin-resistant Staphylococcus aureus in a university hospital setting by using novelsoftware for spa repeat determination and database management. J Clin Microbiol 41, 5442–5448.[CrossRef]
    [Google Scholar]
  34. Harraghy, N., Kormanec, J., Wolz, C., Homerova, D., Goerke,C., Ohlsen, K., Qazi, S., Hill, P. & Herrmann, M. ( 2005; ). sae is essential for expression of the staphylococcal adhesinsEap and Emp. Microbiology 151, 1789–1800.[CrossRef]
    [Google Scholar]
  35. Holmes, A., Ganner, M., McGuane, S., Pitt, T. L., Cookson, B.D. & Kearns, A. M. ( 2005; ). Staphylococcusaureus isolates carrying Panton–Valentine leucocidin genes in Englandand Wales: frequency, characterization, and association with clinical disease. J Clin Microbiol 43, 2384–2390.[CrossRef]
    [Google Scholar]
  36. Holtfreter, S., Grumann, D., Schmudde, M., Nguyen, H. T., Eichler,P., Strommenger, B., Kopron, K., Kolata, J., Giedrys-Kalemba, S. & otherauthors ( 2007; ). Clonal distribution of superantigengenes in clinical Staphylococcus aureus isolates. J ClinMicrobiol 45, 2669–2680.
    [Google Scholar]
  37. Horsburgh, M. J., Aish, J. L., White, I. J., Shaw, L., Lithgow,J. K. & Foster, S. J. ( 2002; ). σ B modulates virulence determinant expression and stress resistance:characterization of a functional rsbU strain derived from Staphylococcusaureus 8325-4. J Bacteriol 184, 5457–5467.[CrossRef]
    [Google Scholar]
  38. Jaffe, A. B. & Hall, A. ( 2005; ).Rho GTPases: biochemistry and biology. Annu Rev Cell Dev Biol 21, 247–269.[CrossRef]
    [Google Scholar]
  39. Karlsson, A. & Arvidson, S. ( 2002; ). Variation in extracellular protease production among clinical isolatesof Staphylococcus aureus due to different levels of expression ofthe protease repressor sarA. Infect Immun 70, 4239–4246.[CrossRef]
    [Google Scholar]
  40. Knobloch, J. K., Jager, S., Horstkotte, M. A., Rohde, H. &Mack, D. ( 2004; ). RsbU-dependent regulation of Staphylococcus epidermidis biofilm formation is mediated via the alternativesigma factor σ B by repression of the negative regulatorgene icaR. Infect Immun 72, 3838–3848.[CrossRef]
    [Google Scholar]
  41. Ladhani, S., Joannou, C. L., Lochrie, D. P., Evans, R. W. &Poston, S. M. ( 1999; ). Clinical, microbial, and biochemicalaspects of the exfoliative toxins causing staphylococcal scalded-skin syndrome. Clin Microbiol Rev 12, 224–242.
    [Google Scholar]
  42. Laemmli, U. K. ( 1970; ). Cleavage of structuralproteins during the assembly of the head of bacteriophage T4. Nature 227, 680–685.[CrossRef]
    [Google Scholar]
  43. Lindsay, J. A. & Foster, S. J. ( 1999; ). Interactive regulatory pathways control virulence determinant productionand stability in response to environmental conditions in Staphylococcusaureus. Mol Gen Genet 262, 323–331.[CrossRef]
    [Google Scholar]
  44. Lindsay, J. A. & Holden, M. T. ( 2006; ). Understanding the rise of the superbug: investigation of the evolutionand genomic variation of Staphylococcus aureus. FunctIntegr Genomics 6, 186–201.
    [Google Scholar]
  45. Livak, K. J. & Schmittgen, T. D. ( 2001; ). Analysis of relative gene expression data using real-time quantitativePCR and the method. Methods 25, 402–408.[CrossRef]
    [Google Scholar]
  46. Lowy, F. D. ( 1998; ). Staphylococcusaureus infections. N Engl J Med 339, 520–532.[CrossRef]
    [Google Scholar]
  47. Mack, D., Bartscht, K., Fischer, C., Rohde, H., de Grahl, C.,Dobinsky, S., Horstkotte, M. A., Kiel, K. & Knobloch, J. K. ( 2001; ). Genetic and biochemical analysis of Staphylococcus epidermidis biofilm accumulation. Methods Enzymol 336, 215–239.
    [Google Scholar]
  48. McAleese, F. M., Walsh, E. J., Sieprawska, M., Potempa, J. &Foster, T. J. ( 2001; ). Loss of clumping factor B fibrinogenbinding activity by Staphylococcus aureus involves cessation of transcription,shedding and cleavage by metalloprotease. J Biol Chem 276, 29969–29978.[CrossRef]
    [Google Scholar]
  49. Mellmann, A., Weniger, T., Berssenbrugge, C., Rothganger, J.,Sammeth, M., Stoye, J. & Harmsen, D. ( 2007; ). BasedUpon Repeat Pattern (BURP): an algorithm to characterize the long-termevolution of Staphylococcus aureus populations based on spapolymorphisms. BMC Microbiol 7, 98 [CrossRef]
    [Google Scholar]
  50. Monecke, S., Slickers, P., Hotzel, H., Richter-Huhn, G., Pohle,M., Weber, S., Witte, W. & Ehricht, R. ( 2006; ).Microarray-based characterisation of a Panton–Valentine leukocidin-positivecommunity-acquired strain of methicillin-resistant Staphylococcus aureus. Clin Microbiol Infect 12, 718–728.[CrossRef]
    [Google Scholar]
  51. Morfeldt, E., Janzon, L., Arvidson, S. & Lofdahl, S. ( 1988; ). Cloning of a chromosomal locus (exp)which regulates the expression of several exoprotein genes in Staphylococcusaureus. Mol Gen Genet 211, 435–440.[CrossRef]
    [Google Scholar]
  52. Murchan, S., Kaufmann, M. E., Deplano, A., de Ryck, R., Struelens,M., Zinn, C. E., Fussing, V., Salmenlinna, S., Vuopio-Varkila, J. & otherauthors ( 2003; ). Harmonization of pulsed-field gelelectrophoresis protocols for epidemiological typing of strains of methicillin-resistant Staphylococcus aureus: a single approach developed by consensus in 10European laboratories and its application for tracing the spread of relatedstrains. J Clin Microbiol 41, 1574–1585.[CrossRef]
    [Google Scholar]
  53. Novick, R. P. ( 1991; ). Genetic systemsin staphylococci. Methods Enzymol 204, 587–636.
    [Google Scholar]
  54. Novick, R. P. ( 2003; ). Autoinductionand signal transduction in the regulation of staphylococcal virulence. Mol Microbiol 48, 1429–1449.[CrossRef]
    [Google Scholar]
  55. Novick, R. P., Ross, H. F., Projan, S. J., Kornblum, J., Kreiswirth,B. & Moghazeh, S. ( 1993; ). Synthesis of staphylococcalvirulence factors is controlled by a regulatory RNA molecule. EMBO J 12, 3967–3975.
    [Google Scholar]
  56. Oscarsson, J., Kanth, A., Tegmark-Wisell, K. & Arvidson,S. ( 2006a; ). SarA is a repressor of hla (α-hemolysin) transcription in Staphylococcus aureus:its apparent role as an activator of hla in the prototype strainNCTC 8325 depends on reduced expression of sarS. J Bacteriol 188, 8526–8533.[CrossRef]
    [Google Scholar]
  57. Oscarsson, J., Tegmark-Wisell, K. & Arvidson, S. ( 2006b; ). Coordinated and differential control of aureolysin (aur) and serine protease (sspA) transcriptionin Staphylococcus aureus by sarA, rot and agr (RNAIII). Int J Med Microbiol 296, 365–380.[CrossRef]
    [Google Scholar]
  58. Peacock, S. J., Moore, C. E., Justice, A., Kantzanou, M., Story,L., Mackie, K., O'Neill, G. & Day, N. P. ( 2002; ). Virulent combinations of adhesin and toxin genes in natural populationsof Staphylococcus aureus. Infect Immun 70, 4987–4996.[CrossRef]
    [Google Scholar]
  59. Peng, H. L., Novick, R. P., Kreiswirth, B., Kornblum, J. &Schlievert, P. ( 1988; ). Cloning, characterization,and sequencing of an accessory gene regulator (agr) in Staphylococcus aureus. J Bacteriol 170, 4365–4372.
    [Google Scholar]
  60. Recsei, P., Kreiswirth, B., O'Reilly, M., Schlievert, P.,Gruss, A. & Novick, R. P. ( 1986; ). Regulation ofexoprotein gene expression in Staphylococcus aureus by agr. Mol Gen Genet 202, 58–61.[CrossRef]
    [Google Scholar]
  61. Sambrook, J., Fritsch, E. F. & Maniatis, T. ( 1989; ). Molecular Cloning: a Laboratory Manual, 2nd edn.Cold Spring Harbor, NY: Cold Spring Harbor Laboratory.
  62. Shaw, L., Golonka, E., Potempa, J. & Foster, S. J. ( 2004; ). The role and regulation of the extracellular proteasesof Staphylococcus aureus. Microbiology 150, 217–228.[CrossRef]
    [Google Scholar]
  63. Sugai, M., Enomoto, T., Hashimoto, K., Matsumoto, K., Matsuo,Y., Ohgai, H., Hong, Y. M., Inoue, S., Yoshikawa, K. & Suginaka, H. ( 1990; ). A novel epidermal cell differentiation inhibitor (EDIN):purification and characterization from Staphylococcus aureus. Biochem Biophys Res Commun 173, 92–98.[CrossRef]
    [Google Scholar]
  64. Sugai, M., Hashimoto, K., Kikuchi, A., Inoue, S., Okumura, H.,Matsumoto, K., Goto, Y., Ohgai, H., Moriishi, K. & other authors ( 1992; ). Epidermal cell differentiation inhibitor ADP-ribosylatessmall GTP-binding proteins and induces hyperplasia of epidermis. J Biol Chem 267, 2600–2604.
    [Google Scholar]
  65. Sung, J. M., Lloyd, D. H. & Lindsay, J. A. ( 2008; ). Staphylococcus aureus host specificity: comparativegenomics of human versus animal isolates by multi-strain microarray. Microbiology 154, 1949–1959.[CrossRef]
    [Google Scholar]
  66. Tenover, F. C., Arbeit, R. D., Goering, R. V., Mickelsen, P.A., Murray, B. E., Persing, D. H. & Swaminathan, B. ( 1995; ). Interpreting chromosomal DNA restriction patterns produced bypulsed-field gel electrophoresis: criteria for bacterial strain typing. J Clin Microbiol 33, 2233–2239.
    [Google Scholar]
  67. Vandenesch, F., Naimi, T., Enright, M. C., Lina, G., Nimmo,G. R., Heffernan, H., Liassine, N., Bes, M., Greenland, T. & other authors ( 2003; ). Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton–Valentine leukocidin genes:worldwide emergence. Emerg Infect Dis 9, 978–984.[CrossRef]
    [Google Scholar]
  68. Wilde, C., Chhatwal, G. S., Schmalzing, G., Aktories, K. &Just, I. ( 2001; ). A novel C3-like ADP-ribosyltransferasefrom Staphylococcus aureus modifying RhoE and Rnd3. JBiol Chem 276, 9537–9542.
    [Google Scholar]
  69. Witte, W., Strommenger, B., Cuny, C., Heuck, D. & Nuebel,U. ( 2007; ). Methicillin-resistant Staphylococcusaureus containing the Panton–Valentine leucocidin gene in Germanyin 2005 and 2006. J Antimicrob Chemother 60, 1258–1263.[CrossRef]
    [Google Scholar]
  70. Wolz, C., McDevitt, D., Foster, T. J. & Cheung, A. L. ( 1996; ). Influence of agr on fibrinogen binding in Staphylococcus aureus Newman. Infect Immun 64, 3142–3147.
    [Google Scholar]
  71. Wolz, C., Pohlmann-Dietze, P., Steinhuber, A., Chien, Y. T.,Manna, A., van Wamel, W. & Cheung, A. ( 2000; ). agr-independent regulation of fibronectin-binding protein(s)by the regulatory locus sar in Staphylococcus aureus. Mol Microbiol 36, 230–243.[CrossRef]
    [Google Scholar]
  72. Yamaguchi, T., Hayashi, T., Takami, H., Ohnishi, M., Murata,T., Nakayama, K., Asakawa, K., Ohara, M., Komatsuzawa, H. & Sugai, M. ( 2001; ). Complete nucleotide sequence of a Staphylococcusaureus exfoliative toxin B plasmid and identification of a novel ADP-ribosyltransferase,EDIN-C. Infect Immun 69, 7760–7771.[CrossRef]
    [Google Scholar]
  73. Yamaguchi, T., Nishifuji, K., Sasaki, M., Fudaba, Y., Aepfelbacher,M., Takata, T., Ohara, M., Komatsuzawa, H., Amagai, M. & Sugai, M. ( 2002a; ). Identification of the Staphylococcus aureusetd pathogenicity island which encodes a novel exfoliative toxin, ETD,and EDIN-B. Infect Immun 70, 5835–5845.[CrossRef]
    [Google Scholar]
  74. Yamaguchi, T., Yokota, Y., Terajima, J., Hayashi, T., Aepfelbacher,M., Ohara, M., Komatsuzawa, H., Watanabe, H. & Sugai, M. ( 2002b; ). Clonal association of Staphylococcus aureus causingbullous impetigo and the emergence of new methicillin-resistant clonal groupsin Kansai district in Japan. J Infect Dis 185, 1511–1516.[CrossRef]
    [Google Scholar]
  75. Yamasaki, O., Tristan, A., Yamaguchi, T., Sugai, M., Lina, G.,Bes, M., Vandenesch, F. & Etienne, J. ( 2006; ).Distribution of the exfoliative toxin D gene in clinical Staphylococcusaureus isolates in France. Clin Microbiol Infect 12, 585–588.[CrossRef]
    [Google Scholar]
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