Skip to main content
SpringerLink
Log in

Quorum quenching is an antivirulence strategy employed by endophytic bacteria

  • Applied microbial and cell physiology
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

Bacteria predominantly use quorum sensing to regulate a plethora of physiological activities such as cell-cell crosstalk, mutualism, virulence, competence, biofilm formation, and antibiotic resistance. In this study, we investigated how certain potent endophytic bacteria harbored in Cannabis sativa L. plants use quorum quenching as an antivirulence strategy to disrupt the cell-to-cell quorum sensing signals in the biosensor strain, Chromobacterium violaceum. We used a combination of high-performance liquid chromatography high-resolution mass spectrometry (HPLC-ESI-HRMSn) and matrix-assisted laser desorption ionization imaging high-resolution mass spectrometry (MALDI-imaging-HRMS) to first quantify and visualize the spatial distribution of the quorum sensing molecules in the biosensor strain, C. violaceum. We then showed, both quantitatively and visually in high spatial resolution, how selected endophytic bacteria of C. sativa can selectively and differentially quench the quorum sensing molecules of C. violaceum. This study provides fundamental insights into the antivirulence strategies used by endophytes in order to survive in their ecological niches. Such defense mechanisms are evolved in order to thwart the plethora of pathogens invading associated host plants in a manner that prevents the pathogens from developing resistance against the plant/endophyte bioactive secondary metabolites. This work also provides evidence towards utilizing endophytes as tools for biological control of bacterial phytopathogens. In continuation, such insights would even afford new concepts and strategies in the future for combating drug resistant bacteria by quorum-inhibiting clinical therapies.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Aly AH, Debbab A, Proksch P (2013) Fungal endophytes—secret producers of bioactive plant metabolites. Pharmazie 68:499–505

    CAS  PubMed  Google Scholar 

  • Amara N, Krom BP, Kaufmann GF, Meijiler MM (2011) Macromolecular inhibition of quorum sensing: enzymes, antibodies, and beyond. Chem Rev 111:195–208

    Article  CAS  PubMed  Google Scholar 

  • Amaral L, Martins A, Spengler G, Molnar J (2014) Efflux pumps of Gram-negative bacteria: what they do, how they do it, with what and how to deal with them. Front Pharmacol 4:168. doi:10.3389/fphar.2013.00168

    Article  PubMed Central  PubMed  Google Scholar 

  • Bjarnholt N, Li B, D’Alvise J, Janfelt C (2014) Mass spectrometry imaging of plant metabolites—principles and possibilities. Nat Prod Rep. doi:10.1039/c3np70100j

    PubMed  Google Scholar 

  • Burmølle M, Thomsen TR, Fazli M, Dige I, Christensen L, Homøe P, Tvede M, Nyvad B, Tolker-Nielsen T, Givskov M, Moser C, Kirketerp-Møller K, Johansen HK, Høiby N, Jensen P, Sørensen SJ, Bjarnsholt T (2010) Biofilms in chronic infections—a matter of opportunity—monospecies biofilms in multispecies infections. FEMS Immmunol Med Microbiol 59:324–336

    Google Scholar 

  • Choo JH, Rukayadi Y, Hwang J-K (2006) Inhibition of bacterial quorum sensing by vanilla extract. Lett Appl Microbiol 42:637–641

    CAS  PubMed  Google Scholar 

  • Christiaen SEA, Matthijs N, Zhang X-H, Nelis HJ, Bossier P, Coenye T (2014) Bacteria that inhibit quorum sensing decrease biofilm formation and virulence in Pseudomonas aeruginosa PAO1. Pathog Dis 70:271–279

    Article  CAS  PubMed  Google Scholar 

  • Claessen D, Rozen DE, Kuipers OP, Søgaard-Andersen L, van Wezel GP (2014) Bacterial solutions to multicellularity: a tale of biofilms, filaments and fruiting bodies. Nat Rev Microbiol. doi:10.1038/nrmicro3178

    PubMed  Google Scholar 

  • Clatworthy AE, Pierson E, Hung DT (2007) Targeting virulence: a new paradigm for antimicrobial therapy. Nat Chem Biol 3:541–548

    Article  CAS  PubMed  Google Scholar 

  • Cornforth DM, Popat R, McNally L, Gurney J, Scott-Phillips TC, Ivens A, Diggle SP, Brown SP (2014) Combinatorial quorum sensing allows bacteria to resolve their social and physical environment. Proc Natl Acad Sci U S A 111:4280–4284

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Galloway WRJD, Hodgkinson JT, Bowden SD, Welch M, Spring DR (2011) Quorum sensing in Gram-negative bacteria: small-molecule modulation of AHL and AI-2 quorum sensing pathways. Chem Rev 111:28–67

    Article  CAS  PubMed  Google Scholar 

  • Grotenhermen F, Müller-Vahl K (2012) The therapeutic potential of Cannabis and cannabinoids. Dtsch Arztebl Int 109:495–501

    PubMed Central  PubMed  Google Scholar 

  • Hosni T, Moretti C, Devescovi G, Suarez-Moreno ZR, Fatmi MB, Guarnaccia C, Pongor S, Onofri A, Buonaurio R, Venturi V (2011) Sharing of quorum-sensing signals and role of interspecies communities in a bacterial plant disease. ISME J 5:1857–1870

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kharwar RN, Mishra A, Gond SK, Stierle A, Stierle D (2011) Anticancer compounds derived from fungal endophytes: their importance and future challenges. Nat Prod Rep 28:1208–1228

    Article  CAS  PubMed  Google Scholar 

  • Kim S-H, Park H-D (2013) Ginger extract inhibits biofilm formation by Pseudomonas aeruginosa PA14. PLoS ONE 8:e76106

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kusari S, Spiteller M (2011) Are we ready for industrial production of bioactive plant secondary metabolites utilizing endophytes? Nat Prod Rep 28:1203–1207

    Article  CAS  PubMed  Google Scholar 

  • Kusari S, Zühlke S, Spiteller M (2009a) An endophytic fungus from Camptotheca acuminata that produces camptothecin and analogues. J Nat Prod 72:2–7

    Article  CAS  PubMed  Google Scholar 

  • Kusari S, Lamshöft M, Spiteller M (2009b) Aspergillus fumigatus Fresenius, an endophytic fungus from Juniperus communis L. Horstmann as a novel source of the anticancer pro-drug deoxypodophyllotoxin. J Appl Microbiol 107:1019–1030

    Article  CAS  PubMed  Google Scholar 

  • Kusari S, Hertweck C, Spiteller M (2012) Chemical ecology of endophytic fungi: origins of secondary metabolites. Chem Biol 19:792–798

    Article  CAS  PubMed  Google Scholar 

  • Kusari P, Kusari S, Spiteller M, Kayser O (2013) Endophytic fungi harbored in Cannabis sativa L.: diversity and potential as biocontrol agents against host plant-specific phytopathogens. Fungal Divers 60:137–151

    Article  Google Scholar 

  • Kusari S, Singh S, Jayabaskaran C (2014) Biotechnological potential of plant-associated endophytic fungi: hope versus hype. Trends Biotechnol. doi:10.1016/j.tibtech.2014.03.009

    Google Scholar 

  • Lane DJ (1991) 16S/23S rRNA sequencing. In: Stackebrandt E, Goodfellow M (eds) Nucleic acid techniques in bacterial systematics. Wiley, New York, pp 115–175

    Google Scholar 

  • LaSarre B, Federle MJ (2013) Exploiting quorum sensing to confuse bacterial pathogens. Microbiol Mol Biol Rev 77:73–111

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lau YY, Sulaiman J, Chen JW, Yin W-F, Chan K-G (2013) Quorum sensing activity of Enterobacter asburiae isolated from lettuce leaves. Sensors 13:14189–14199

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Limsuwan S, Voravuthikunchai SP (2008) Boesenbergia pandurata (Roxb.) Schltr., Eleutherine americana Merr. and Rhodomyrtus tomentosa (Aiton) Hassk. as antibiofilm producing and antiquorum sensing in Streptococcus pyogenes. FEMS Immunol Med Microbiol 53:429–436

    Article  CAS  PubMed  Google Scholar 

  • Márquez LM, Redman RS, Rodriguez RJ, Roossinck MJ (2007) A virus in a fungus in a plant: three‑way symbiosis required for thermal tolerance. Science 315:513–515

    Article  PubMed  Google Scholar 

  • McClean KH, Winson MK, Fish L, Taylor A, Chhabra SR, Camara M, Daykin M, Lamb JH, Swift S, Bycroft BW, Stewart GSAB, Williams P (1997) Quorum sensing and Chromobacterium violeceum: exploitation of violacein production and inhibition for the detection of N-acyl homoserine lactones. Microbiology 143:3703–3711

    Article  CAS  PubMed  Google Scholar 

  • Morohoshi T, Fukamachi K, Kato M, Kato N, Ikeda T (2010) Regulation of the violacein biosynthetic gene cluster by acylhomoserine lactone-mediated quorum sensing in Chromobacterium violaceum ATCC 12472. Biosci Biotechnol Biochem 74:2116–2119

    Article  CAS  PubMed  Google Scholar 

  • Morohoshi T, Tokita K, Ito S, Saito Y, Maeda S, Kato N, Ikeda T (2013) Inhibition of quorum sensing in gram-negative bacteria by alkylamine-modified cyclodextrins. J Biosci Bioeng 116:175–179

    Article  CAS  PubMed  Google Scholar 

  • O’Loughlin CT, Miller LC, Siryaporn A, Drescher K, Semmelhack MF, Bassler BL (2013) A quorum-sensing inhibitor blocks Pseudomonas aeruginosa virulence and biofilm formation. Proc Natl Acad Sci U S A 110:17981–17986

    Article  PubMed Central  PubMed  Google Scholar 

  • Ou CC, Lu TM, Tsai JJ, Yen JH, Chen HW, Lin MY (2009) Antioxidative effect of lactic acid bacteria: intact cells vs. intracellular extracts. J Food Drug Anal 17:209–216

    Google Scholar 

  • Porras-Alfaro A, Bayman P (2011) Hidden fungi, emergent properties: endophytes and microbiomes. Annu Rev Phytopathol 49:291–315

    Article  CAS  PubMed  Google Scholar 

  • Rasko DA, Sperandio V (2010) Anti-virulence strategies to combat bacteria-mediated disease. Nat Rev Drug Discov 9:117–128

    Article  CAS  PubMed  Google Scholar 

  • Rishi P, Preet S, Kaur P (2011) Effect of L. plantarum cell-free extract and co-trimoxazole against Salmonella typhimurium: a possible adjunct therapy. Ann Clin Microbiol Antimicrob 10:9

    Article  PubMed Central  PubMed  Google Scholar 

  • Rompp A, Spengler B (2013) Mass spectrometry imaging with high resolution in mass and space. Histochem Cell Biol 139:759–783

    Article  PubMed Central  PubMed  Google Scholar 

  • Safari M, Amache R, Esmaeilishirazifard E, Keshavarz T (2014) Microbial metabolism of quorum-sensing molecules acyl-homoserine lactones, γ-heptalactone and other lactones. Appl Microbiol Biotechnol 98:3401–3412

    Article  CAS  PubMed  Google Scholar 

  • Samoilova Z, Muzyka N, Lepekhina E, Oktyabrsky O, Smirnova G (2014) Medicinal plant extracts can variously modify biofilm formation in Escherichia coli. A Van Leeuw J Microb 105:709–722

    Article  CAS  Google Scholar 

  • Schafhauser J, Lepine F, McKay G, Ahlgren HG, Khakimova M, Nguyen D (2014) The stringent response modulates 4-hydroxy-2-alkylquinoline biosynthesis and quorum-sensing hierarchy in Pseudomonas aeruginosa. J Bacteriol 196:1641–1650

    Article  CAS  PubMed  Google Scholar 

  • Schulz B, Guske S, Dammann U, Boyle C (1998) Endophyte-host interactions II. Defining symbiosis of the endophyte-host interaction. Symbiosis 25:213–227

    Google Scholar 

  • Shih C-J, Chen P-Y, Liaw C-C, Lai Y-M, Yang Y-L (2014) Bringing microbial interactions to light using imaging mass spectrometry. Nat Prod Rep. doi:10.1039/c3np70091g

    PubMed  Google Scholar 

  • Sifri CD (2008) Quorum sensing: bacteria talk sense. Clin Infect Dis 47:1070–1076

    Article  CAS  PubMed  Google Scholar 

  • Taura F, Sirikantaramas S, Shoyamaa Y, Shoyamaa Y, Morimotoa S (2007) Phytocannabinoids in Cannabis sativa: recent studies on biosynthetic enzymes. Chem Biodivers 4:1649–1663

    Article  CAS  PubMed  Google Scholar 

  • Teplitski M, Mathesius U, Rumbaugh KP (2011) Perception and degradation of N-acyl homoserine lactone quorum sensing signals by mammalian and plant cells. Chem Rev 111:100–116

    Article  CAS  PubMed  Google Scholar 

  • Thenmozhi R, Nithyanand P, Rathna J, Pandian SK (2009) Antibiofillm activity of coral-associated bacteria against different clinical M serotypes of Streptococcus pyogenes. FEMS Immunol Med Microbiol 57:284–294

    Article  CAS  PubMed  Google Scholar 

  • Zhao Q, Mutukumira A, Lee SJ, Maddox I, Shu Q (2011) Functional properties of free and encapsulated Lactobacillus reuteri DPC16 during and after passage through a simulated gastrointestinal tract. World J Microbiol Biotechnol 28:61–70

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This research was funded by the Ministry of Innovation, Science and Research of the German Federal State North Rhine-Westphalia (NRW) and TU Dortmund by a scholarship to P.K. from the CLIB-Graduate Cluster Industrial Biotechnology. We thank the German Research Foundation (DFG) for financing the MALDI imaging high-resolution mass spectrometers. We are thankful to Federal Institute for Drugs and Medical Devices (Bundesinstituts für Arzneimittel und Medizinprodukte, BfArM), Bonn, Germany for granting us the necessary permissions for working with Cannabis plants (BtM number 458 49 89). S.K. was a Visiting Researcher at the Department of Plant Sciences, University of Oxford, South Parks Road, Oxford OX1 15 3RB, UK, during part of the work and preparation of the manuscript (Apr 2013 to Mar 2014). S.K. gratefully acknowledges M.S. for approving and authorizing, Dr. Gail M. Preston for hosting, and TU Dortmund for supporting his stay at the University of Oxford.

Conflict of Interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Biochemical and Chemical Engineering, TU Dortmund, Emil-Figge-Str. 66, 44227, Dortmund, Germany

    Parijat Kusari & Oliver Kayser

  2. Institute of Environmental Research (INFU), Department of Chemistry and Chemical Biology, TU Dortmund, Otto-Hahn-Str. 6, 44221, Dortmund, Germany

    Souvik Kusari, Marc Lamshöft, Selahaddin Sezgin & Michael Spiteller

Authors
  1. Parijat Kusari
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Souvik Kusari
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marc Lamshöft
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Selahaddin Sezgin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michael Spiteller
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Oliver Kayser
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Michael Spiteller or Oliver Kayser.

Additional information

Souvik Kusari and Marc Lamshöft contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kusari, P., Kusari, S., Lamshöft, M. et al. Quorum quenching is an antivirulence strategy employed by endophytic bacteria. Appl Microbiol Biotechnol 98, 7173–7183 (2014). https://doi.org/10.1007/s00253-014-5807-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00253-014-5807-3

Keywords

Search

Navigation