Skip to main content

Advertisement

SpringerLink
Log in

In Vitro Modulation of E. coli Community Behavior and Human Innate Immune System by Lantibiotic Nisin

  • Published:
International Journal of Peptide Research and Therapeutics Aims and scope Submit manuscript

Abstract

Biofilms are microbial communities with genetically divergent microorganisms. Such communal behavior is known to provide survival benefit to the unicellular organisms in adverse conditions. Pathogenicity of opportunistic bacterial pathogens largely depends on their success in proper quorum establishment and biofilm formation. Thus molecules causing quorum-sensing attenuation, preventing the biofilm formation or instigating preformed biofilm dislodgement could serve as attractive drugs/drug supplements. Here we investigate the effect of nisin—type A lantibiotic naturally produced by Lactococcus lactis—on laboratory developed Escherichia coli biofilms and on isolated human neutrophils. Activity evaluation was done on the biofilms of clinical isolates of E. coli, developed on glass slides in a simple static bioreactor design. Nisin not only inhibited the formation but also effectively dislodged the preformed E. coli biofilms developed on glass surfaces. Presence of nisin also demonstrated a significant decrease in the expression of E. coli virulence factors viz. hemolysin and curli expression. The microorganisms dislodged from the biofilms and set free in the circulation of infected host might later reassociate to form new biofilms after nisin clearance from circulation. Thus complete eradication of infective bacterium will depend on stimulatory effect of nisin (if any) on human immune system cells. Therefore modulation of human neutrophil activity by nisin was also evaluated. Presence of nisin induced neutrophil extracellular trap (NET) formation or NETosis in a manner similar to that demonstrated by LPS (lipopolysaccharide) in vitro. Our results thus present nisin as a plausible molecule to be used in treatment of chronic bacterial infections as it indicated increased fitness for the same.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

Abbreviations

AMP:

Antimicrobial peptide

BIC:

Biofilm inhibitory concentration

CR:

Congo Red

DMSO:

Dimethyl sulfoxide

HBSS:

Hanks’ balance salt solution

LPS:

Lipopolysaccharide

NET:

Neutrophil extracellular trap

NBT:

Nitroblue tetrazolium

PMN:

Polymorphonuclear neutrophils

PBS:

Phosphate buffered saline

PMA:

Phorbol-12-myristate-13-acetate

ROS:

Reactive oxygen species

References

  • Aida Y, Pabst MJ (1990) Priming of neutrophils by lipopolysaccharide for enhanced release of superoxide. Requirement for plasma but not for tumor necrosis factor-alpha. J Immunol 145(9):3017–3025

    PubMed  CAS  Google Scholar 

  • Barnhart MM, Chapman MR (2006) Curli biogenesis and function. Annu Rev Microbiol 60:131–147

    Article  PubMed  CAS  Google Scholar 

  • Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, Weinrauch Y, Zychlinsky A (2004) Neutrophil extracellular traps kill bacteria. Science 303(5663):1532–1535

    Article  PubMed  CAS  Google Scholar 

  • Choi HS, Kim JW, Cha YN, Kim C (2006) A quantitative nitroblue tetrazolium assay for determining intracellular superoxide anion production in phagocytic cells. J Immunoassay Immunochem 27(1):31–44

    Article  PubMed  CAS  Google Scholar 

  • Christianson DW (2006) Biochemistry. Five golden rings. Science 311(5766):1382–1383

    Article  PubMed  CAS  Google Scholar 

  • Dang PM-C, Stensballe A, Boussetta T, Raad H, Dewas C, Kroviarski Y, Hayem G, Jensen ON, Gougerot-Pocidalo M-A, El-Benna J (2006) A specific p47phox-serine phosphorylated by convergent MAPKs mediates neutrophil NADPH oxidase priming at inflammatory sites. J Clin Investig 116(7):2033–2043

    Article  PubMed  CAS  Google Scholar 

  • de Kievit TR, Iglewski BH (2000) Bacterial quorum sensing in pathogenic relationships. Infect Immun 68(9):4839–4849

    Article  PubMed  Google Scholar 

  • Delves-Broughton J (2005) Nisin as a food preservative, vol 57 No. 12. Australian Institute of Food Science and Technology, North Sydney

    Google Scholar 

  • Edwards SW (1996) The O-2 generating NADPH oxidase of phagocytes: structure and methods of detection. Methods 9(3):563–577

    Article  PubMed  CAS  Google Scholar 

  • Felmlee T, Welch RA (1988) Alterations of amino acid repeats in the Escherichia coli hemolysin affect cytolytic activity and secretion. Proc Natl Acad Sci USA 85(14):5269–5273

    Article  PubMed  CAS  Google Scholar 

  • Fuchs TA, Abed U, Goosmann C, Hurwitz R, Schulze I, Wahn V, Weinrauch Y, Brinkmann V, Zychlinsky A (2007) Novel cell death program leads to neutrophil extracellular traps. J Cell Biol 176(2):231–241

    Article  PubMed  CAS  Google Scholar 

  • Gophna U, Barlev M, Seijffers R, Oelschlager TA, Hacker J, Ron EZ (2001) Curli fibers mediate internalization of Escherichia coli by eukaryotic cells. Infect Immun 69(4):2659–2665

    Article  PubMed  CAS  Google Scholar 

  • Hall-Stoodley L, Stoodley P (2009) Evolving concepts in biofilm infections. Cell Microbiol 11(7):1034–1043

    Article  PubMed  CAS  Google Scholar 

  • Hammar M, Bian Z, Normark S (1996) Nucleator-dependent intercellular assembly of adhesive curli organelles in Escherichia coli. Proc Natl Acad Sci USA 93(13):6562–6566

    Article  PubMed  CAS  Google Scholar 

  • Hsu ST, Breukink E, Tischenko E, Lutters MA, de Kruijff B, Kaptein R, Bonvin AM, van Nuland NA (2004) The nisin-lipid II complex reveals a pyrophosphate cage that provides a blueprint for novel antibiotics. Nat Struct Mol Biol 11(10):963–967

    Article  PubMed  CAS  Google Scholar 

  • Irie Y, Parsek MR (2008) Quorum sensing and microbial biofilms. In: Romeo T (ed) Bacterial biofilms. Current topics in microbiology and immunology, vol 322. Springer, Berlin, pp 67–84. doi:10.1007/978-3-540-75418-3_4

    Google Scholar 

  • Kleerebezem M, Quadri LE (2001) Peptide pheromone-dependent regulation of antimicrobial peptide production in Gram-positive bacteria: a case of multicellular behavior. Peptides 22(10):1579–1596

    Article  PubMed  CAS  Google Scholar 

  • Li P, Li M, Lindberg MR, Kennett MJ, Xiong N, Wang Y (2010) PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps. J Exp Med 207(9):1853–1862

    Article  PubMed  CAS  Google Scholar 

  • McCoy AJ, Liu H, Falla TJ, Gunn JS (2001) Identification of Proteus mirabilis mutants with increased sensitivity to antimicrobial peptides. Antimicrob Agents Chemother 45(7):2030–2037

    Article  PubMed  CAS  Google Scholar 

  • Naghmouchi K, Drider D, Baah J, Teather R (2010) Nisin A and polymyxin B as synergistic inhibitors of Gram-positive and Gram-negative bacteria. Probiotics Antimicrob Proteins 2(2):98–103. doi:10.1007/s12602-009-9033-8

    Article  CAS  Google Scholar 

  • O’Toole G, Kaplan HB, Kolter R (2000) Biofilm formation as microbial development. Annu Rev Microbiol 54:49–79

    Article  PubMed  Google Scholar 

  • Olasupo NA, Fitzgerald DJ, Gasson MJ, Narbad A (2003) Activity of natural antimicrobial compounds against Escherichia coli and Salmonella enterica serovar Typhimurium. Lett Appl Microbiol 37(6):448–451. doi:10.1046/j.1472-765X.2003.01427.x

    Article  PubMed  CAS  Google Scholar 

  • Parsek MR, Singh PK (2003) Bacterial biofilms: an emerging link to disease pathogenesis. Annu Rev Microbiol 57:677–701

    Article  PubMed  CAS  Google Scholar 

  • Phelps HA, Neely MN (2007) SalY of the Streptococcus pyogenes lantibiotic locus is required for full virulence and intracellular survival in macrophages. Infect Immun 75(9):4541–4551. doi:10.1128/iai.00518-07

    Article  PubMed  CAS  Google Scholar 

  • Raina S, De Vizio D, Odell M, Clements M, Vanhulle S, Keshavarz T (2009) Microbial quorum sensing: a tool or a target for antimicrobial therapy? Biotechnol Appl Biochem 54(2):65–84

    Article  PubMed  CAS  Google Scholar 

  • Rasmussen TB, Givskov M (2006) Quorum sensing inhibitors: a bargain of effects. Microbiology 152(4):895–904. doi:10.1099/mic.0.28601-0

    Article  PubMed  CAS  Google Scholar 

  • Reddy KV, Aranha C, Gupta SM, Yedery RD (2004) Evaluation of antimicrobial peptide nisin as a safe vaginal contraceptive agent in rabbits: in vitro and in vivo studies. Reproduction 128(1):117–126

    Article  PubMed  CAS  Google Scholar 

  • Reunanen J, Saris PE (2009) Survival of nisin activity in intestinal environment. Biotechnol Lett 31(8):1229–1232

    Article  PubMed  CAS  Google Scholar 

  • Shpakov A (2009) Peptide autoinducers in bacteria. Microbiology 78(3):255–266. doi:10.1134/s0026261709030011

    Article  CAS  Google Scholar 

  • Shrout J, Parsek M (2006) Quorum sensing: coordinating group behavior through intercellular signals. In: Nickerson CA, Schurr MJ (eds) Molecular paradigms of infectious disease. Emerging infectious diseases of the 21st century. Springer, New York, pp 404–437. doi:10.1007/978-0-387-32901-7_11

    Google Scholar 

  • Steinberg BE, Grinstein S (2007) Unconventional roles of the NADPH oxidase: signaling, ion homeostasis, and cell death. Sci STKE 2007(379):pe11. doi:10.1126/stke.3792007pe11

    Article  PubMed  Google Scholar 

  • Yost CC, Cody MJ, Harris ES, Thornton NL, McInturff AM, Martinez ML, Chandler NB, Rodesch CK, Albertine KH, Petti CA, Weyrich AS, Zimmerman GA (2009) Impaired neutrophil extracellular trap (NET) formation: a novel innate immune deficiency of human neonates. Blood 113(25):6419–6427. doi:10.1182/blood-2008-07-171629

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We would like to acknowledge University Grants Commission, India, for providing financial sanction for the study and would also like to thank Dr. Dipti Christian, Principal, Hislop College, Nagpur, for making all the necessary infrastructural facilities available.

Author information

Authors and Affiliations

  1. Hislop School of Biotechnology, Hislop College, Temple Road, Civil Lines, Nagpur, 440001, Maharashtra, India

    Deovrat N. Begde, Sunita B. Bundale, Mashitha V. Pise, Jaishree A. Rudra, Nandita A. Nashikkar & Avinash A. Upadhyay

Authors
  1. Deovrat N. Begde
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sunita B. Bundale
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mashitha V. Pise
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jaishree A. Rudra
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nandita A. Nashikkar
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Avinash A. Upadhyay
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Avinash A. Upadhyay.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Begde, D.N., Bundale, S.B., Pise, M.V. et al. In Vitro Modulation of E. coli Community Behavior and Human Innate Immune System by Lantibiotic Nisin. Int J Pept Res Ther 18, 171–183 (2012). https://doi.org/10.1007/s10989-012-9290-3

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10989-012-9290-3

Keywords

Search

Navigation