, Volume 86, Issue 5, pp 571–582 | Cite as

Suppression of development of vancomycin-resistant Staphylococcus epidermidis by low-molecular-weight cationic peptides of the lantibiotic family

  • L. I. Kononova
  • L. B. Filatova
  • D. V. Eroshenko
  • V. P. Korobov
Experimental Articles


Low-molecular-weight cationic peptides warnerin and hominin activate the autolytic systems and cause cell death of Staphylococcus epidermidis 33 GISK, as well as its vancomycin-resistant variant. Minimal bactericidal concentrations of warnerin for both strains studied were determined. Efficiency of antibacterial action of the peptide was found to depend directly on its concentration. Comparative investigation of adhesive properties and biofilm-forming ability of two strains was carried out. The cationic peptide warnerin was found to suppress biofilm formation by both vancomycin-sensitive and resistant strains of S. epidermidis 33 GISK and to have a pronounced destructuring effect on formed biofilms.


Staphylococcus epidermidis warnerin hominin minimal inhibitory concentration minimal bactericidal concentration adhesion biofilms 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Amorena, B., Gracia, E., Monzon, M., Leiva, J., Oteiza, C., Perez, M., Alabart, J.-L., and Hernández-Yago, J., Antibiotic susceptibility assay for Staphylococcus aureus in biofilms developed in vitro, J. Antimicrob. Chemother., 1999, vol. 44, pp. 43–55.CrossRefPubMedGoogle Scholar
  2. Antunes, A.L.S., Trentin, D.S., Bonfanti, J.W., Pinto, C.C.F., Perez, L.R.R., Macedo, A.J., and Barth, A.L., Application of a feasible method for determination of biofilm antimicrobial susceptibility in staphylococci,, 2010, vol. 118, pp. 873–877.Google Scholar
  3. Atlas, R.M., Handbook of Microbiological Media, CRC, 1993.Google Scholar
  4. Chaignon, P., Sadovskaya, I., Ragunah, C., Ramasubbu, N., Kaplan, J.B., and Jabbouri, S., Susceptibility of staphylococcal biofilms to enzymatic treatments depends on their chemical composition, Appl. Microbiol. Biotechnol., 2007, vol. 75, pp. 125–132.CrossRefPubMedGoogle Scholar
  5. Chebotar’, I.V., Mayanskii, N.A., and Kinchakova, E.D., A new method for investigation of antibiotic resistance of bacterial biofilms, Klin. Mikrobiol. Antimikrob. Khimioter., 2012, vol. 14, no. 4, pp. 303–308.Google Scholar
  6. Desbois, A.P., Gemmell, C.G., and Coote, P.J., In vivo efficacy of the antimicrobial peptide ranalexin in combination with the endopeptidase lysostaphin against wound and systemic methicillin-resistant Staphylococcus aureus (MRSA) infections, Int. J. Antimicrob. Agents, 2010, vol. 35, pp. 559–565.CrossRefPubMedGoogle Scholar
  7. Eroshenko, D.V. and Korobov, V.P., New AMPs from Staphylococcus spp., warnerin and hominin, reduce Staphylocococcus epidermidis adhesion and biofilm formation, in Multidisciplinary Approach for Studying and Combating Microbial Pathogens, Mendez-Vilas, A., Ed., Brown Walker, 2015, pp. 98–101.Google Scholar
  8. Filatova, L.B., Lemkina, L.M., Kononova, L.I., Polyudova, T.V., and Korobov, V.P., Antibacterial action of a cationic peptide warnerin is mediated by activation of autolytic systems of attacked bacteria, Proc. Perm. Univ., 2010. no. 1 (1), pp. 32–35.Google Scholar
  9. Fritsche, T.R., Rhomberga, P.R., Sadera, H.S., and Jones, R.N., In vitro activity of omiganan pentahydrochloride tested against vancomycin-tolerant,-intermediate, and-resistant Staphylococcus aureus, Diagn. Microbiol. Infect. Dis., 2008, vol. 60, pp. 399–403.CrossRefPubMedGoogle Scholar
  10. Gazzola, S. and Cocconcelli, P.S., Vancomycin heteroresistance and biofilm formation in Staphylococcus epidermidis from food, Microbiology (UK), 2008, vol. 154, pp. 3224–3231.CrossRefGoogle Scholar
  11. Gutiérrez, D., Ruas-Madiedo, P., Martínez, B., Rodríguez, A., and García, P., Effective removal of staphylococcal biofilms by the endolysin LysH5, PLoS One, 2014, vol. 9, no. 9, pp. 1–8.CrossRefGoogle Scholar
  12. Hernandes, C., da Silva Coppede, J., Bertoni, B.W., de Castro França, S., and Soares Pereira, A.M., Flash microbiocide: a rapid and economic method for determination of MBC and MFC, Am. J. Plant Sci., 2013, vol. 4, pp. 850–852.CrossRefGoogle Scholar
  13. Jain, A. and Agarwal, A., Biofilm production, a marker of pathogenic potential of colonizing and commensal staphylococci, J. Microbiol. Methods, 2009, vol. 76, pp. 88–92.CrossRefPubMedGoogle Scholar
  14. Kononova, L.I. and Korobov, V.P., Changes in the biological properties of Staphylococcus epidermidis 33 in the course of development of vancomycin resistance, Proc. Samara Sci. Center, Russ. Acad. Sci., 2011, vol. 13, no. 5 (3), pp. 152–155.Google Scholar
  15. Kononova, L.I. and Korobov, V.P., Physiological properties of the vancomycin-resistant strain Staphylococcus epidermidis 33 GISK VANR, Microbiology (Moscow), 2015, vol. 84, no. 1, pp. 50–57.CrossRefGoogle Scholar
  16. Korobov, V.P., Lemkina, L.M., Filatova, L.B., and Polyudova, T.V., Degradation of the biofilms of coagulose-negative staphylococci by a cationic peptide warnerin, Proc. Samara Sci. Center, Russ. Acad. Sci., 2011, vol. 13, no. 5 (3), pp. 156–159.Google Scholar
  17. Korobov, V.P., Lemkina, L.M., Polyudova, T.V., and Akimenko, V.K., Isolation and characterization of a new lowmolecular antibacterial peptide of the lantibiotics family, Microbiology (Moscow), 2010, vol. 79, pp. 206–215.CrossRefGoogle Scholar
  18. Lepeuple, A.S., Van Gemert, E., and Chapot-Chartier, M.P., Analysis of the bacteriolytic enzymes of the autolytic Lactococcus lactis subsp. cremoris strain AM2 by renaturing polyacrylamide gel electrophoresis: identification of a prophage-encoded enzyme, Appl. Environ. Microbiol., 1998, vol. 64, no. 11, pp. 4142–4148.PubMedPubMedCentralGoogle Scholar
  19. Levison, M.E., Pharmacodynamics of antimicrobial drugs, Infect. Dis. Clin. North Am., 2004, vol. 18, pp. 451–465.CrossRefPubMedGoogle Scholar
  20. Methods for Determining Bactericidal Activity of Antimicrobial Agents; Approved Guideline, Clinical and laboratory standards institute (CLSI), M26-A, Wayne, 1999.Google Scholar
  21. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Clinical and laboratory standards institute (CLSI), 2012.Google Scholar
  22. Micek, S.T., Alternatives to vancomycin for the treatment of methicillin-resistant Staphylococcus aureus infections, Clin. Infect. Dis., 2007, vol. 45, pp. 184–190.CrossRefGoogle Scholar
  23. Moskowitz, S.M., Foster, J.M., Emerson, J., and Burns, J.L., Clinically feasible biofilm susceptibility assay for isolates of Pseudomonas aeruginosa from patients with cystic fibrosis, J. Clin. Microbiol., 2004, vol. 42, pp. 1915–1922.CrossRefPubMedPubMedCentralGoogle Scholar
  24. Otto, M., Molecular basis of Staphylococcus epidermidis infections, Semin. Immunopathol., 2012, vol. 34, no. 5, pp. 201–214.CrossRefPubMedGoogle Scholar
  25. Peterson, L.R. and Shanholtzer, C.J., Tests for bactericidal effects of antimicrobial agents: technical performance and clinical relevance, Clin. Microbiol. Rev., 1992, vol. 5, no. 4, pp. 420–432.CrossRefPubMedPubMedCentralGoogle Scholar
  26. RF Patent no. 2528055 C2, 2014.Google Scholar
  27. Sadekuzzaman, M., Yang, S., Mizan, M.F.R., and Ha, S.D., Current and recent advanced strategies for combating biofilms, Compr. Rev. Food Sci. Food Saf., 2015, vol. 14, pp. 491–509.CrossRefGoogle Scholar
  28. Stepanović, S., Vuković, D., Hola, V., Di Bonaventura, G., Djukić, S., Ćirković, I., and Ruzicka, F., Quantification of biofilm in microtiter plates: overview of testing conditions and practical recommendations for assessment of biofilm production by staphylococci, Apmis, 2007, vol. 115, pp. 891–899.CrossRefPubMedGoogle Scholar
  29. Van Bambeke, F., Mingeot-Leclercq, M.P., Struelens, M.J., and Tulkens, P.M., The bacterial envelope as a target for novel anti-MRSA antibiotics, Trends Pharmacol. Sci., 2008, vol. 29, no. 3, pp. 124–134.CrossRefPubMedGoogle Scholar
  30. Venkatesh, M., Rong, L., Raad, I., and Versalovic, J., Novel synergistic antibiofilm combinations for salvage of infected catheters, J. Med. Microbiol., 2009, vol. 58, pp. 936–944.CrossRefPubMedGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2017

Authors and Affiliations

  • L. I. Kononova
    • 1
  • L. B. Filatova
    • 1
  • D. V. Eroshenko
    • 1
  • V. P. Korobov
    • 1
    • 2
    • 3
  1. 1.Institute of Ecology and Genetics of Microorganisms, Ural BranchRussian Academy of SciencesPermRussia
  2. 2.Perm State UniversityPermRussia
  3. 3.Perm National Research Polytechnic UniversityPermRussia

Personalised recommendations