Skip to main content
Log in

Bactericidal Activity and Synergy Studies of Peptide AP-CECT7121 Against Multi-resistant Bacteria Isolated from Human and Animal Soft Tissue Infections

  • Published:
Probiotics and Antimicrobial Proteins Aims and scope Submit manuscript

Abstract

AP-CECT7121 is an antimicrobial peptide, produced by Enterococcus faecalis CECT7121, with bactericidal activity against Gram-positive bacteria. The aim of this study was to evaluate the bactericidal activity of AP-CECT7121, alone and with gentamicin, against multi-resistant bacteria isolated from human and animals with soft tissue infections. During the period 2014–2015, bacterial strains producing human and animal soft tissue infections were studied. Samples from patients attended at a general hospital and cattle from four dairies in the Province of Buenos Aires (Argentina) were included. Twenty-two methicillin-resistant Staphylococcus aureus (11, human blood samples; 11, cow milk) and five vancomycin-resistant Ent. faecium strains isolated from four mastitic dairy cows were tested. AP-CECT7121 (12 mg/L) potency was assessed by time-kill curves alone or with sub-inhibitory concentrations of gentamicin. All staphylococcal strains were susceptible to gentamicin; enterococci did not show high-level gentamicin resistance. Colony counts were carried out at 0, 2, 4, 8, and 24 h of incubation. AP-CECT7121 showed bactericidal activity against all the enterococcal strains. In addition, AP-CECT7121 had a bactericidal effect on most staphylococci (16/22). Early AP-CECT7121/gentamicin synergy (4–8 h) for all staphylococci was detected. At 24 h, synergy (19/22) and indifference (3/22) were observed. Synergy with gentamicin was detected for staphylococci. AP-CECT7121 constitutes an attractive candidate for its use as a natural therapeutic tool for the treatment of infections produced by multi-resistant Staph. aureus and vancomycin-resistant Ent. faecium isolated from humans and animals.

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.

Similar content being viewed by others

References

  1. Pyörälä S (2009) Treatment of mastitis during lactation. Ir Vet J 62:40–44

    Article  Google Scholar 

  2. Contreras GA, Rodríguez JM (2011) Mastitis: comparative etiology and epidemiology. J Mammary Gland Biol Neoplasia 16:339–356

    Article  Google Scholar 

  3. Canton R, Horcajada JP, Oliver A, Ruiz Garbajosa P, Vila J (2013) Inappropiate use of antibiotics in hospitals: the complex relationship between antibiotic use and antimicrobial resistance. Enferm Infecc Microbiol Clin 31:3–11

    Article  Google Scholar 

  4. Lee TC, Carrick MM, Scott BG, Hodges JC, Pham HQ (2007) Incidence and clinical characteristics of methicillin-resistant Staphylococcus aureus necrotizing fasciitis in a large urban hospital. Am J Surg 194:809–812

    Article  Google Scholar 

  5. David MZ, Daum RS (2010) Community-associated methicillin-resistant Staphylococcus aureus: epidemiology and clinical consequences of an emerging epidemic. Clin Microbiol Rev 23:616–687

    Article  CAS  Google Scholar 

  6. Becker K, Ballhausen B, Kahl BC, Köck R (2017) The clinical impact of livestock-associated methicillin-resistant Staphylococcus aureus of the clonal complex 398 for humans. Vet Microbiol 200:33–38

    Article  Google Scholar 

  7. Hammerum AM (2012) Enterococci of animal origin and their significance for public health. Clin Microbiol Infect 18:619–625

    Article  CAS  Google Scholar 

  8. Chambers HF (1997) Methicilin resistance in staphylococci: molecular and biochemical basis and clinical implications. Clin Microbiol Rev 10:781–791

    CAS  Google Scholar 

  9. Cercenado E (2011) Enterococcus: phenotype and genotype resistence and epidemiology in Spain. Enferm Infecc Microbiol Clin 29:59–65

    Article  Google Scholar 

  10. Ray GT, Suaya JA, Baxter R (2013) Incidence, microbiology, and patient characteristics of skin and soft-tissue infections in a U.S. population: a retrospective population-based study. BMC Infect Dis 13:252

    Article  Google Scholar 

  11. Acuña L, Morero RD, Bellomio A (2011) Development of wide-spectrum hybrid bacteriocins for food biopreservation. Food Bioprocess Technol 4:1029–1049

    Article  Google Scholar 

  12. Sparo M, Nuñez GG, Castro M, Calcagno ML, García Allende MA, Ceci M, Najle R, Manghi M (2008) Characteristics of an environmental strain, Enterococcus faecalis CECT7121 and its effects as additive on craft dry-fermented sausages. Food Microbiol 25:607–615

    Article  CAS  Google Scholar 

  13. Sparo M (2006) Investigation of bacteriocins from lactic acid bacteria in Tandil District. Ph.D. thesis. University of Buenos Aires, Argentina. In Spanish.

  14. Winn WC, Allen SD, Janda WM, Koneman EW, Procop GW, Schreckenberger PC, Woods GL (2008). Koneman. Diagnóstico microbiológico. 6ª ed. Editorial Médica Panamericana, Buenos Aires

  15. Clinical and Laboratory Standards Institute (2016) Performance standards for antimicrobial susceptibility testing, 26th informational supplement. M100-S26. CLSI, Wayne, PA

  16. Sparo MD, Jones DG, Sánchez Bruni SF (2009) Assessment of the in vitro efficacy of the novel antimicrobial peptide CECT7121 against human Gram-positive bacteria from serious infections refractory to treatment. Chemotherapy 55:270–277

    Article  CAS  Google Scholar 

  17. Dawson RMC, Elliot DC, Elliot WH, Jones KM (1969) Data for biochemical research, 2nd edn. Oxford University Press, Oxford

    Google Scholar 

  18. Krapp C, Moody JA (1992) Timed kill assay for determining synergy. In: Isenberg HD ed. ASM Manual of Clinical Microbiology. ASM Press, Washington DC

  19. Lester CH, Frimodt-Møller N, Lund Sorensen T, Monnet DL, Hammerum AM (2006) In vivo transfer of the vanA resistance gene from an Enterococcus faecium isolate of animal origin to an E. faecium isolate of human origin in the intestine of human volunteers. Antimicrob Agents Chemother 50:596–599

    Article  CAS  Google Scholar 

  20. de Niederhäusern S, Bondi M, Messi P, Iseppi R, Sabia C, Manicardi G, Anacarso I (2011) Vancomycin resistance transferability from VanA enterococci to Staphylococcus aureus. Curr Microbiol 62:1363–1367

    Article  Google Scholar 

  21. Delpech G, Pourcel G, Schell C, de Luca M, Basualdo J, Bernstein J, Grenovero S, Sparo M (2012) Antimicrobial resistance profiles of Enterococcus faecalis and Enterococcus faecium isolated from artisanal food of animal origin in Argentina. Foodborne Pathog Dis 9:939–944

    Article  CAS  Google Scholar 

  22. Li S, Li J, Qiao Y, Ning X, Zeng T, Shen X (2014) Prevalence and invasiveness of community-acquired methicillin-resistant Staphylococcus aureus: a meta-analysis. Indian J Pathol Microbiol 57:418–422

    Article  Google Scholar 

  23. Hammami R, Fernandez B, Lacroix C, Fliss I (2013) Anti-infective properties of bacteriocins: an update. Cell Mol Life Sci 70:2947–2967

    Article  CAS  Google Scholar 

  24. Cao LT, Wu JQ, Xie F, Hu SH, Mo Y (2007) Efficacy of nisin in treatment of clinical mastitis in lactating dairy cows. J Dairy Sci 90:3980–3985

    Article  CAS  Google Scholar 

  25. Hassan M, Kjos M, Nes IF, Diep DB, Loftipour F (2012) Natural antimicrobial peptides from bacteria: characteristics and potential applications to fight against antibiotic resistance. J Appl Microbiol 113:723–736

    Article  CAS  Google Scholar 

  26. Varella Coelho ML, Santos Nascmento JD, Fagundes PC, Madureira DJ, Oliveira SS, Vasconcelos de Paiva Brito MA, Freire Bastos M (2007) Activity of staphylococcal bacteriocins against Staphylococcus aureus and Streptococcus agalactiae involved in bovine mastitis. Res Microbiol 158:625–630

    Article  Google Scholar 

  27. Okuda KI, Zendo T, Sugimoto S, Iwase T, Tajima A, Yamada S, Sonomoto K, Mizunoe Y (2013) Effects of bacteriocins on methicillin-resistant Staphylococcus aureus biofilm. Antimicrob Agents Chemother 57:5572–5579

    Article  CAS  Google Scholar 

  28. Severina E, Severin A, Tomasz A (1998) Antibacterial efficacy of nisin against multidrug-resistant Grampositive pathogens. J Antimicorb Chemother 41:341–347

    Article  CAS  Google Scholar 

  29. Aumpad R, Na-Bangchang K (2007) Pumilicin 4, a novel bacteriocin with anti-MRSA and anti-VRE activity produced by newly isolated bacteria Bacillus pumilus strain WAPB4. Curr Microbiol 55:308–313

    Article  Google Scholar 

  30. Al Atya AK, Belguesmia Y, Chataigne G, Ravallec R, Vachée A, Szunerits S, Boukherroub R, Drider D (2016) Anti-MRSA activities of enterocins DD28 and DD93 and evidences on their role in the inhibition of biofilm formation. Front Microbiol 7:817

    Article  Google Scholar 

  31. Kaur G, Singh TP, Malik RK, Bhardwaj A, De S (2014) Antibacterial efficacy of nisin, pediocin 34 and enterocin FH99 against L. monocytogenes, E. faecium and E. faecalis and bacteriocin cross resistance and antibiotic susceptibility of their bacteriocin resistant variants. J Food Sci Technol 51:233–244

    Article  CAS  Google Scholar 

  32. Swartz MN (2004) Clinical practice. Cellulitis. N Engl J Med 350:904–912

    Article  CAS  Google Scholar 

  33. Ki V, Rotstein C (2008) Bacterial skin and soft tissue infections in adults: a review of their epidemiology, pathogenesis, diagnosis, treatment and site of care. Can J Infect Dis Med Microbiol 19:173–184

    Google Scholar 

  34. Dombrowski JC, Winston LG (2008) Clinical failures of appropriately-treated methicillin-resistant Staphylococcus aureus infections. J Inf Secur 57:110–115

    Google Scholar 

  35. Fernández L, Delgado S, Herrera H, Maldonado A, Rodríguez JM (2008) The bacteriocin Nisin, an effective agent for the treatment of staphylococcal mastitis during lactation. J Hum Lact 24:311–316

    Article  Google Scholar 

  36. Piper C, Draper LA, Coter PD, Ross RP, Hill C (2009) A comparison of the activities of lacticin 3147 and nisin against drug-resistant Staphylococcus aureus and Enterococcus species. J Antimicrob Chemother 64:546–551

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mónica Sparo.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Funding

This study was funded by the Consejo Interuniveristario Nacional (PDTS CIN-CONICET 2014 # 85), Buenos Aires, Argentina.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Delpech, G., Bistoletti, M., Ceci, M. et al. Bactericidal Activity and Synergy Studies of Peptide AP-CECT7121 Against Multi-resistant Bacteria Isolated from Human and Animal Soft Tissue Infections. Probiotics & Antimicro. Prot. 9, 355–362 (2017). https://doi.org/10.1007/s12602-017-9289-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12602-017-9289-3

Keywords

Navigation