Skip to main content
Log in

Effect of amino acid substitution in the staphylococcal peptides warnericin RK and PSMα on their anti-Legionella and hemolytic activities

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Warnericin RK from Staphylococcus warneri and PSMα from Staphylococcus epidermidis are anti-Legionella peptides which were differently classified in a previous study according to their mode of action. Indeed, warnericin RK is highly hemolytic with a bactericidal mode of action, whereas PSMα is poorly hemolytic with a bacteriostatic mode of action toward L. pneumophila. In order to find anti-Legionella peptides which are not hemolytic, a collection of peptides varying in sequence from warnericin RK to PSMα were designed and synthesized, and their anti-Legionella activities, in terms of growth inhibition, permeabilization, and bactericidal effect, as well as their hemolytic activities, were measured and compared. The results showed that some residues, at position 14 for both peptides for instance, were of major importance for bactericidal and hemolytic activities.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Fields BS, Benson RF, Besser RE (2002) Legionella and Legionnaires’ disease: 25 years of investigation. Clin Microbiol Rev 15:506–526

    PubMed Central  PubMed  Google Scholar 

  2. Control ECfDPa (2014) Legionnaires’ disease surveillance in Europe, 2012. Stockholm: ECDC. http://ecdc.europa.eu/en/publications/Publications//legionnaires-disease-surveillance-2012.pdf. Accessed March 2014

  3. Molmeret M, Bitar DM, Han L, Kwaik YA (2004) Cell biology of the intracellular infection by Legionella pneumophila. Microbes Infect 6:129–139

    CAS  PubMed  Google Scholar 

  4. Borella P, Guerrieri E, Marchesi I, Bondi M, Messi P (2005) Water ecology of Legionella and protozoan: environmental and public health perspectives. Biotechnol Annu Rev 11:355–380

    CAS  PubMed  Google Scholar 

  5. Thomas V, Bouchez T, Nicolas V, Robert S, Loret JF, Levi Y (2004) Amoebae in domestic water systems: resistance to disinfection treatments and implication in Legionella persistence. J Appl Microbiol 97:950–963

    CAS  PubMed  Google Scholar 

  6. Marchand A, Verdon J, Lacombe C, Crapart S, Hechard Y, Berjeaud JM (2011) Anti-Legionella activity of staphylococcal hemolytic peptides. Peptides 32:845–851

    Article  CAS  PubMed  Google Scholar 

  7. Dinges MM, Orwin PM, Schlievert PM (2000) Exotoxins of Staphylococcus aureus. Clin Microbiol Rev 13:16–34 table of contents

    PubMed Central  CAS  PubMed  Google Scholar 

  8. Verdon J, Girardin N, Lacombe C, Berjeaud JM, Hechard Y (2009) delta-hemolysin, an update on a membrane-interacting peptide. Peptides 30:817–823

    Article  CAS  PubMed  Google Scholar 

  9. Hechard Y, Ferraz S, Bruneteau E, Steinert M, Berjeaud JM (2005) Isolation and characterization of a Staphylococcus warneri strain producing an anti-Legionella peptide. FEMS Microbiol Lett 252:19–23

    CAS  PubMed  Google Scholar 

  10. Mehlin C, Headley CM, Klebanoff SJ (1999) An inflammatory polypeptide complex from Staphylococcus epidermidis: isolation and characterization. J Exp Med 189:907–918

    PubMed Central  CAS  PubMed  Google Scholar 

  11. Vuong C, Otto M (2002) Staphylococcus epidermidis infections. Microbes Infect 4:481–489

    PubMed  Google Scholar 

  12. Yao Y, Sturdevant DE, Otto M (2005) Genomewide analysis of gene expression in Staphylococcus epidermidis biofilms: insights into the pathophysiology of S. epidermidis biofilms and the role of phenol-soluble modulins in formation of biofilms. J Infect Dis 191:289–298

    CAS  PubMed  Google Scholar 

  13. Verdon J, Falge M, Maier E, Bruhn H, Steinert M, Faber C, Benz R, Hechard Y (2009) Detergent-like activity and alpha-helical structure of warnericin RK, an anti-Legionella peptide. Biophys J 97:1933–1940

    PubMed Central  CAS  PubMed  Google Scholar 

  14. Brogden KA (2005) Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat Rev Microbiol 3:238–250

    CAS  PubMed  Google Scholar 

  15. Yeaman MR, Yount NY (2003) Mechanisms of antimicrobial peptide action and resistance. Pharmacol Rev 55:27–55

    CAS  PubMed  Google Scholar 

  16. Matsuzaki K, Murase O, Fujii N, Miyajima K (1996) An antimicrobial peptide, magainin 2, induced rapid flip-flop of phospholipids coupled with pore formation and peptide translocation. Biochemistry 35:11361–11368

    Article  CAS  PubMed  Google Scholar 

  17. Matsuzaki K, Sugishita K, Fujii N, Miyajima K (1995) Molecular basis for membrane selectivity of an antimicrobial peptide, magainin 2. Biochemistry 34:3423–3429

    Article  CAS  PubMed  Google Scholar 

  18. Pouny Y, Rapaport D, Mor A, Nicolas P, Shai Y (1992) Interaction of antimicrobial dermaseptin and its fluorescently labeled analogues with phospholipid membranes. Biochemistry 31:12416–12423

    Article  CAS  PubMed  Google Scholar 

  19. Bechinger B, Lohner K (2006) Detergent-like actions of linear amphipathic cationic antimicrobial peptides. Biochim Biophys Acta 1758:1529–1539

    CAS  PubMed  Google Scholar 

  20. Verdon J, Berjeaud JM, Lacombe C, Hechard Y (2008) Characterization of anti-Legionella activity of warnericin RK and delta-lysin I from Staphylococcus warneri. Peptides 29:978–984

    Article  CAS  PubMed  Google Scholar 

  21. Alouf JE, Dufourcq J, Siffert O, Thiaudiere E, Geoffroy C (1989) Interaction of staphylococcal delta-toxin and synthetic analogues with erythrocytes and phospholipid vesicles. Biological and physical properties of the amphipathic peptides. Eur J Biochem 183:381–390

    CAS  PubMed  Google Scholar 

  22. Dhople VM, Nagaraj R (2005) Conformation and activity of delta-lysin and its analogs. Peptides 26:217–225

    Article  CAS  PubMed  Google Scholar 

  23. Kerr ID, Dufourcq J, Rice JA, Fredkin DR, Sansom MS (1995) Ion channel formation by synthetic analogues of staphylococcal delta-toxin. Biochim Biophys Acta 1236:219–227

    PubMed  Google Scholar 

  24. Matsuzaki K, Sugishita K, Harada M, Fujii N, Miyajima K (1997) Interactions of an antimicrobial peptide, magainin 2, with outer and inner membranes of gram-negative bacteria. Biochim Biophys Acta 1327:119–130

    CAS  PubMed  Google Scholar 

  25. Tossi A, Sandri L, Giangaspero A (2000) Amphipathic, alpha-helical antimicrobial peptides. Biopolymers 55:4–30

    Article  CAS  PubMed  Google Scholar 

  26. Wimley WC, White SH (1996) Experimentally determined hydrophobicity scale for proteins at membrane interfaces. Nat Struct Biol 3:842–848

    CAS  PubMed  Google Scholar 

  27. Bessalle R, Kapitkovsky A, Gorea A, Shalit I, Fridkin M (1990) All-D-magainin: chirality, antimicrobial activity and proteolytic resistance. FEBS Lett 274:151–155

    CAS  PubMed  Google Scholar 

  28. Wade D, Boman A, Wahlin B, Drain CM, Andreu D, Boman HG, Merrifield RB (1990) All-D amino acid-containing channel-forming antibiotic peptides. Proc Natl Acad Sci USA 87:4761–4765

    PubMed Central  CAS  PubMed  Google Scholar 

  29. Dathe M, Meyer J, Beyermann M, Maul B, Hoischen C, Bienert M (2002) General aspects of peptide selectivity towards lipid bilayers and cell membranes studied by variation of the structural parameters of amphipathic helical model peptides. Biochim Biophys Acta 1558:171–186

    CAS  PubMed  Google Scholar 

  30. Uematsu N, Matsuzaki K (2000) Polar angle as a determinant of amphipathic alpha-helix-lipid interactions: a model peptide study. Biophys J 79:2075–2083

    PubMed Central  CAS  PubMed  Google Scholar 

  31. Pokorny A, Almeida PF (2004) Kinetics of dye efflux and lipid flip-flop induced by delta-lysin in phosphatidylcholine vesicles and the mechanism of graded release by amphipathic, alpha-helical peptides. Biochemistry 43:8846–8857

    Article  CAS  PubMed  Google Scholar 

  32. Pokorny A, Birkbeck TH, Almeida PF (2002) Mechanism and kinetics of delta-lysin interaction with phospholipid vesicles. Biochemistry 41:11044–11056

    Article  CAS  PubMed  Google Scholar 

  33. Laabei M, Jamieson WD, Yang Y, van den Elsen J, Jenkins AT (2014) Investigating the lytic activity and structural properties of Staphylococcus aureus phenol soluble modulin (PSM) peptide toxins. Biochim Biophys Acta 1838:3153–3161. doi:10.1016/j.bbamem.2014.08.026

    CAS  PubMed  Google Scholar 

  34. Eisenberg D, Schwarz E, Komaromy M, Wall R (1984) Analysis of membrane and surface protein sequences with the hydrophobic moment plot. J Mol Biol 179:125–142

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

A. Marchand was supported by a grant from the French Minister of Research. We thank Dr. Thierry Jouenne who provided the first synthetic peptides used in our study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jean-Marc Berjeaud.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Marchand, A., Augenstreich, J., Loiseau, C. et al. Effect of amino acid substitution in the staphylococcal peptides warnericin RK and PSMα on their anti-Legionella and hemolytic activities. Mol Cell Biochem 405, 159–167 (2015). https://doi.org/10.1007/s11010-015-2407-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-015-2407-1

Keywords

Navigation