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High prevalence of edin-C encoding RhoA-targeting toxin in clinical isolates of Staphylococcus aureus

  • P. Munro
  • R. Clément
  • J.-P. Lavigne
  • C. Pulcini
  • E. LemichezEmail author
  • L. LandraudEmail author
Article

Abstract

Staphylococcus aureus, a major causative agent of human infection, produces a large array of virulence factors, including various toxins. Among them, the host RhoA GTPase ADP-ribosylating EDIN toxins are considered as potential virulence factors. Using the polymerase chain reaction (PCR) assay, we analyzed the virulence profile of 256 S. aureus isolates from various clinical sites of infections. We developed specific primers to detect the three isoforms of edin-encoding genes. We found a prevalence of 14% (36 bacteria) of edin-encoding genes among these clinical isolates. Strikingly, we found that 90% of all edin-bearing S. aureus isolates carried the type-C allele. Both the spa types and the profile of virulence factors of these edin-positive isolates are highly variable. Notably, we show for the first time that edin-C-positive isolates were more frequently recovered from deep-seated infections than other types of infections. Our present work, thus, strongly suggests that the presence of edin-C is a risk factor of S. aureus dissemination in tissues and, thus, represents a predictive marker for a pejorative evolution of staphylococcal infections.

Keywords

Fusidic Acid Staphylococcal Enterotoxin Clonal Origin Aureus Isolate Enterotoxin Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

We are grateful to Fernand Girard-Pipau and Prof. Claire Poyart for providing the various strains of Staphylococcus aureus and Prof. Jean-Louis Mege for the critical reading of the manuscript.

Our laboratory is supported by an institutional funding from the INSERM and a grant from the Agence Nationale de la Recherche (ANR R07113AS) and the Association pour la Recherche sur le Cancer (ARC 4906).

References

  1. 1.
    Lowy FD (1998) Staphylococcus aureus infections. N Engl J Med 339(8):520–532PubMedCrossRefGoogle Scholar
  2. 2.
    Fournier B, Philpott DJ (2005) Recognition of Staphylococcus aureus by the innate immune system. Clin Microbiol Rev 18(3):521–540PubMedCrossRefGoogle Scholar
  3. 3.
    Becker K, Friedrich AW, Lubritz G et al (2003) Prevalence of genes encoding pyrogenic toxin superantigens and exfoliative toxins among strains of Staphylococcus aureus isolated from blood and nasal specimens. J Clin Microbiol 41(4):1434–1439PubMedCrossRefGoogle Scholar
  4. 4.
    Boquet P, Lemichez E (2003) Bacterial virulence factors targeting Rho GTPases: parasitism or symbiosis? Trends Cell Biol 13(5):238–246PubMedCrossRefGoogle Scholar
  5. 5.
    Dinges MM, Orwin PM, Schlievert PM (2000) Exotoxins of Staphylococcus aureus. Clin Microbiol Rev 13(1):16–34PubMedCrossRefGoogle Scholar
  6. 6.
    Wilde C, Aktories K (2001) The Rho-ADP-ribosylating C3 exoenzyme from Clostridium botulinum and related C3-like transferases. Toxicon 39(11):1647–1660PubMedCrossRefGoogle Scholar
  7. 7.
    Wilde C, Vogelsgesang M, Aktories K (2003) Rho-specific Bacillus cereus ADP-ribosyltransferase C3cer cloning and characterization. Biochemistry 42(32):9694–9702PubMedCrossRefGoogle Scholar
  8. 8.
    Chardin P, Boquet P, Madaule P et al (1989) The mammalian G protein rhoC is ADP-ribosylated by Clostridium botulinum exoenzyme C3 and affects actin microfilaments in Vero cells. EMBO J 8(4):1087–1092PubMedGoogle Scholar
  9. 9.
    Aktories K, Barbieri JT (2005) Bacterial cytotoxins: targeting eukaryotic switches. Nat Rev Microbiol 3(5):397–410PubMedCrossRefGoogle Scholar
  10. 10.
    Jaffe AB, Hall A (2005) Rho GTPases: biochemistry and biology. Annu Rev Cell Dev Biol 21:247–269PubMedCrossRefGoogle Scholar
  11. 11.
    Visvikis O, Maddugoda MP, Lemichez E (2010) Direct modifications of Rho proteins: deconstructing GTPase regulation. Biol Cell 102(7):377–389PubMedCrossRefGoogle Scholar
  12. 12.
    Boyer L, Doye A, Rolando M et al (2006) Induction of transient macroapertures in endothelial cells through RhoA inhibition by Staphylococcus aureus factors. J Cell Biol 173(5):809–819PubMedCrossRefGoogle Scholar
  13. 13.
    Lemichez E, Lecuit M, Nassif X et al (2010) Breaking the wall: targeting of the endothelium by pathogenic bacteria. Nat Rev Microbiol 8(2):93–104PubMedGoogle Scholar
  14. 14.
    Rolando M, Munro P, Stefani C et al (2009) Injection of Staphylococcus aureus EDIN by the Bacillus anthracis protective antigen machinery induces vascular permeability. Infect Immun 77(9):3596–3601PubMedCrossRefGoogle Scholar
  15. 15.
    Munro P, Benchetrit M, Nahori MA et al (2010) The Staphylococcus aureus epidermal cell differentiation inhibitor toxin promotes formation of infection foci in a mouse model of bacteremia. Infect Immun 78(8):3404–3411PubMedCrossRefGoogle Scholar
  16. 16.
    Inoue S, Sugai M, Murooka Y et al (1991) Molecular cloning and sequencing of the epidermal cell differentiation inhibitor gene from Staphylococcus aureus. Biochem Biophys Res Commun 174(2):459–464PubMedCrossRefGoogle Scholar
  17. 17.
    Franke GC, Böckenholt A, Sugai M et al (2010) Epidemiology, variable genetic organization and regulation of the EDIN-B toxin in Staphylococcus aureus from bacteraemic patients. Microbiology 156(3):860–872PubMedCrossRefGoogle Scholar
  18. 18.
    Yamaguchi T, Hayashi T, Takami H et al (2001) Complete nucleotide sequence of a Staphylococcus aureus exfoliative toxin B plasmid and identification of a novel ADP-ribosyltransferase, EDIN-C. Infect Immun 69(12):7760–7771PubMedCrossRefGoogle Scholar
  19. 19.
    Czech A, Yamaguchi T, Bader L et al (2001) Prevalence of Rho-inactivating epidermal cell differentiation inhibitor toxins in clinical Staphylococcus aureus isolates. J Infect Dis 184(6):785–788PubMedCrossRefGoogle Scholar
  20. 20.
    Ben Nejma M, Mastouri M, Bel Hadj Jrad B et al (2008) Characterization of ST80 Panton–Valentine leukocidin-positive community-acquired methicillin-resistant Staphylococcus aureus clone in Tunisia. Diagn Microbiol Infectious Dis (in press) [Epub ahead of print]Google Scholar
  21. 21.
    O’Neill AJ, Larsen AR, Skov R et al (2007) Characterization of the epidemic European fusidic acid-resistant impetigo clone of Staphylococcus aureus. J Clin Microbiol 45(5):1505–1510PubMedCrossRefGoogle Scholar
  22. 22.
    Bauer AW, Kirby WM, Sherris JC et al (1966) Antibiotic susceptibility testing by a standardized single disk method. Am J Clin Pathol 45(4):493–496PubMedGoogle Scholar
  23. 23.
    Harmsen D, Claus H, Witte W et al (2003) Typing of methicillin-resistant Staphylococcus aureus in a university hospital setting by using novel software for spa repeat determination and database management. J Clin Microbiol 41(12):5442–5448PubMedCrossRefGoogle Scholar
  24. 24.
    Yamaguchi T, Yokota Y, Terajima J et al (2002) Clonal association of Staphylococcus aureus causing bullous impetigo and the emergence of new methicillin-resistant clonal groups in Kansai district in Japan. J Infect Dis 185(10):1511–1516PubMedCrossRefGoogle Scholar
  25. 25.
    Tristan A, Ying L, Bes M et al (2003) Use of multiplex PCR to identify Staphylococcus aureus adhesins involved in human hematogenous infections. J Clin Microbiol 41(9):4465–4467PubMedCrossRefGoogle Scholar
  26. 26.
    Petersson AC, Olsson-Liljequist B, Miörner H et al (2010) Evaluating the usefulness of spa typing, in comparison with pulsed-field gel electrophoresis, for epidemiological typing of methicillin-resistant Staphylococcus aureus in a low-prevalence region in Sweden 2000–2004. Clin Microbiol Infect 16(5):456–462PubMedCrossRefGoogle Scholar
  27. 27.
    Holtfreter S, Bauer K, Thomas D et al (2004) egc-Encoded superantigens from Staphylococcus aureus are neutralized by human sera much less efficiently than are classical staphylococcal enterotoxins or toxic shock syndrome toxin. Infect Immun 72(7):4061–4071PubMedCrossRefGoogle Scholar
  28. 28.
    Johnson WM, Tyler SD, Ewan EP et al (1991) Detection of genes for enterotoxins, exfoliative toxins, and toxic shock syndrome toxin 1 in Staphylococcus aureus by the polymerase chain reaction. J Clin Microbiol 29(3):426–430PubMedGoogle Scholar
  29. 29.
    Jarraud S, Mougel C, Thioulouse J et al (2002) Relationships between Staphylococcus aureus genetic background, virulence factors, agr groups (alleles), and human disease. Infect Immun 70(2):631–641PubMedCrossRefGoogle Scholar
  30. 30.
    Lina G, Boutite F, Tristan A et al (2003) Bacterial competition for human nasal cavity colonization: role of Staphylococcal agr alleles. Appl Environ Microbiol 69(1):18–23PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  1. 1.INSERM, U895, C3M, Toxines Microbiennes dans la Relation Hôte PathogènesUniversité de Nice-Sophia-Antipolis, UFR Médecine, IFR50NiceFrance
  2. 2.Université de Nice-Sophia-Antipolis, UFR Médecine, IFR50NiceFrance
  3. 3.Service d’InfectiologieHôpital l’Archet 1Nice Cedex 3France
  4. 4.INSERM, Espri 26Université Montpellier 1, UFR de MédecineNîmesFrance
  5. 5.Laboratoire de BactériologieCHU CaremeauNîmesFrance
  6. 6.Laboratoire de BactériologieCHU de Nice, Hôpital l’ArchetNiceFrance

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