Caenorhabditis elegans as an In Vivo Non-Mammalian Model System to Study Quorum Sensing in Pathogens



Indiscriminate use of antibiotics has led to the emergence of multiple drug-resistant pathogens. Quorum sensing (QS) is an intercellular communication system which is widely present in pathogens regulating the virulence genes expression and pathogenesis in host. Interruption of QS regulatory system is an attractive strategy to attenuate pathogens’ virulence. Several synthetic and natural compounds with potential QS inhibitory activity have been identified and tested in vitro for their inhibitory activity. To study the in vivo efficacy of the compounds, a model organism is required. Unlike other vertebrate model organisms like mouse or rabbit, C. elegans has emerged as a simple, amenable, genetically tractable worm for studying QS inhibitory activity of compounds. This chapter focuses on the advantages and recent development in using C. elegans as a non-mammalian in vivo model system.


Quorum Sensing Quorum Sensing Inhibitor Quorum Sensing Regulation Quorum Sensing Signalling Molecule Slow Killing 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Aballay A, Yorgey P, Ausubel FM (2000) Salmonella typhimurium proliferates and establishes a persistent infection in the intestine of Caenorhabditis elegans. Curr Biol 10:1539–1542. doi: 10.1016/S0960-9822(00)00830-7 PubMedCrossRefGoogle Scholar
  2. Adonizio A, Ausubel FM, Mathee K (2008) Attenuation of Pseudomonas aeruginosa virulence by medicinal plants in a Caenorhabditis elegans model system. J Med Microbiol 57:809–813. doi: 10.1099/jmm.0.47802-0 PubMedCrossRefGoogle Scholar
  3. Albuquerque P, Casadevall A (2012) Quorum sensing in fungi – a review. Med Mycol 50:337–345. doi: 10.3109/13693786.2011.652201 PubMedCrossRefGoogle Scholar
  4. Ausubel FM, Rahme LG, Tan MW, Le L, Wong SM, Tompkins RG, Calderwood SB (1997) Use of model plant hosts to identify Pseudomonas aeruginosa virulence factors. Proc Natl Acad Sci USA 94:13245–13250PubMedCrossRefPubMedCentralGoogle Scholar
  5. Brackman G, Cos P, Maes L, Nelis HJ, Coenye T (2011) Quorum sensing inhibitors increase the susceptibility of bacterial biofilms to antibiotics in vitro and in vivo. Antimicrob Agents Chemother 55:2655–2661. doi: 10.1128/AAC.00045-11 PubMedCrossRefPubMedCentralGoogle Scholar
  6. Cezairliyan B, Vinayavekhin N, Grenfell-Lee D, Yuen GJ, Saghatelian A, Ausuble FM (2013) Identification of Pseudomonas aeruginosa phenazines that kill Caenorhabditis elegans. PLoS Pathog 9:e1003101. doi: 10.1371/journal.ppat.1003101 PubMedCrossRefPubMedCentralGoogle Scholar
  7. Chen H, Fujita M, Feng Q, Clardy J, Fink GR (2004) Tyrosol is a quorum-sensing molecule in Candida albicans. Proc Natl Acad Sci USA 101:5048–5052. doi: 10.1073/pnas.0401416101 PubMedCrossRefPubMedCentralGoogle Scholar
  8. Corsi AK (2006) A biochemists guide to C. elegans. Anal Biochem 359:1–17. doi: 10.1016/j.ab.2006.07.033 PubMedCrossRefPubMedCentralGoogle Scholar
  9. Darby C, Cosma CL, Thomas JH, Manoil C (1999) Lethal paralysis of Caenorhabditis elegans by Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 96:15202–15207. doi: 10.1073/pnas.96.26.15202 PubMedCrossRefPubMedCentralGoogle Scholar
  10. Dzidic S, Bedekovic V (2003) Horizontal gene transfer-emerging multidrug resistance in hospital bacteria. Acta Pharmacol Sin 24:519–526PubMedGoogle Scholar
  11. Epstein AC, Gleadle JM, McNeill LA, Hewitson KS, O’Rourke J, Mole DR, Mukherji M, Metzen E, Wilson MI, Dhanda A, Tian YM, Masson N, Hamilton DL, Jaakkola P, Barstead R, Hodgkin J, Maxwell PH, Pugh CW, Schofield CJ, Ratcliffe PJ (2001) C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell 107:43–54. doi: 10.1016/S0092-8674(01)00507-4 PubMedCrossRefGoogle Scholar
  12. Fazly A, Jain C, Dehner AC, Issi L, Lilly EA, Ali A, Cao H, Fidel PL Jr, Rao RP, Kaufman PD (2013) Chemical screening identifies filastatin, a small molecule inhibitor of Candida albicans adhesion, morphogenesis, and pathogenesis. Proc Natl Acad Sci USA 110:13594–13599. doi: 10.1073/pnas.1305982110 PubMedCrossRefPubMedCentralGoogle Scholar
  13. Gallagher LA, Manoil C (2001) Pseudomonas aeruginosa PAO1 kills Caenorhabditis elegans by cyanide poisoning. J Bacteriol 183:6207–6214. doi: 10.1128/JB.183.21.6207-6214.2001 PubMedCrossRefPubMedCentralGoogle Scholar
  14. Husain FM, Ahmad I, Asif M, Tahseen Q (2013) Influence of clove oil on certain quorum-sensing-regulated functions and biofilm of Pseudomonas aeruginosa and Aeromonas hydrophila. J Biosci 38:835–844. doi: 10.1007/s12038-013-9385-9 PubMedCrossRefGoogle Scholar
  15. Kirienko NV, Kirienko DR, Larkins-Ford J, Wählby C, Ruvkun G, Ausubel FM (2013) Pseudomonas aeruginosa disrupts Caenorhabditis elegans iron homeostasis, causing a hypoxic response and death. Cell Host Microbe 13:406–416. doi: 10.1016/j.chom.2013.03.003 PubMedCrossRefPubMedCentralGoogle Scholar
  16. Kong C, Yehye WA, Rahman NA, Tan MW, Nathan S (2014) Discovery of potential anti-infectives against Staphylococcus aureus using a Caenorhabditis elegans infection model. BMC Complement Altern Med 14:4. doi: 10.1186/1472-6882-14-4 PubMedCrossRefPubMedCentralGoogle Scholar
  17. Köthe M, Antl M, Huber B, Stoecker K, Ebrecht D, Steinmetz I, Eberl L (2003) Killing of Caenorhabditis elegans by Burkholderia cepacia is controlled by the cep quorum-sensing system. Cell Microbiol 5:343–351. doi: 10.1046/j.1462-5822.2003.00280.x PubMedCrossRefGoogle Scholar
  18. Lee KM, Lim J, Nam S, Yoon MY, Kwon YK, Jung BY, Park Y, Park S, Yoon SS (2011) Inhibitory effect of broccoli extract on Escherichia coli O157:H7 quorum sensing and in vivo virulence. FEMS Microbiol Lett 321:67–74. doi: 10.1111/j.1574-6968 PubMedCrossRefGoogle Scholar
  19. Lowry F (1998) Staphylococcus aureus infections. N Engl J Med 339:520–532CrossRefGoogle Scholar
  20. Maeda T, García-Contreras R, Pu M, Sheng L, Garcia LR, Tomás M, Wood TK (2012) Quorum quenching quandary: resistance to antivirulence compounds. ISME J 6:493–501. doi: 10.1038/ismej.2011 PubMedCrossRefPubMedCentralGoogle Scholar
  21. Mahajan-Miklos S, Tan MW, Rahme LG, Ausubel FM (1999) Molecular mechanisms of bacterial virulence elucidated using a Pseudomonas aeruginosa-Caenorhabditis elegans pathogenesis model. Cell 96:47–56PubMedCrossRefGoogle Scholar
  22. Manefield M, Rasmussen TB, Henzter M, Andersen JB, Steinberg P, Kjelleberg S, Givskov M (2002) Halogenated furanones inhibit quorum sensing through accelerated LuxR turnover. Microbiology 148:1119–1127PubMedGoogle Scholar
  23. Moy TI, Conery AL, Ford LJ, Wu G, Mazitschek R, Casadei G, Lewis K, Carpenter AE, Ausuble FM (2009) High-throughput screen for novel antimicrobials using a whole animal infection model. ACS Chem Biol 4:527–533. doi: 10.1021/cb900084v PubMedCrossRefPubMedCentralGoogle Scholar
  24. Murono K, Hirano Y, Koyano S, Ito K, Fujieda K (2003) Molecular comparison of bacterial isolates from blood with strains colonizing pharynx and intestine in immuno-compromised patients with sepsis. J Med Microbiol 52:527–530. doi: 10.1099/jmm.0.05076-0 PubMedCrossRefGoogle Scholar
  25. Nealson KH, Platt T, Hastings JW (1970) The cellular control of the synthesis and activity of the bacterial luminescent system. J Bacteriol 104:313–322PubMedPubMedCentralGoogle Scholar
  26. Okoli I, Coleman JJ, Tampakakis E, An WF, Holson E, Wagner F, Conery AL, Larkins-Ford J, Wu G, Stern A, Ausubel FM, Mylonakis E (2009) Identification of antifungal compounds active against Candida albicans using an improved high-throughput Caenorhabditis elegans assay. PLoS One 4:e7025. doi: 10.1371/journal.pone.0007025 PubMedCrossRefPubMedCentralGoogle Scholar
  27. O’Loughlin CT, Miller LC, Siryaporn A, Drescher K, Semmelhack MF, Bassler LB (2013) A quorum-sensing inhibitor blocks Pseudomonas aeruginosa virulence and biofilm formation. Proc Natl Acad Sci USA 110:17981–17986. doi: 10.1073/pnas.1316981110 PubMedCrossRefPubMedCentralGoogle Scholar
  28. Oncul O, Ulkur E, Acar A, Turhan V, Yeniz E, Karacaer Z, Yildiz F (2009) Prospective analysis of nosocomial infections in a burn care unit, Turkey. Indian J Med Res 130:758–764PubMedGoogle Scholar
  29. Papaioannou E, Wahjudi M, Nadal-Jimenez P, Koch G, Setroikromo R, Quax WJ (2009) Quorum-quenching acylase reduces the virulence of Pseudomonas aeruginosa in a Caenorhabditis elegans infection model. Antimicrob Agents Chemother 53:4891–4897. doi: 10.1128/AAC.00380-09 PubMedCrossRefPubMedCentralGoogle Scholar
  30. Peleg AY, Tampakakis E, Fuchs BB, Eliopoulos GM, Moellering RC Jr, Mylonakis E (2008) Prokaryote-eukaryote interactions identified by using Caenorhabditis elegans. Proc Natl Acad Sci USA 105:14585–14590. doi: 10.1073/pnas.0805048105 PubMedCrossRefPubMedCentralGoogle Scholar
  31. Rasmussen TB, Manefield M, Andersen JB, Eberl L, Anthoni U, Christophersen C, Steinberg P, Kjelleberg S, Givsko VM (2000) How Delisea pulchra furanones affect quorum sensing and swarming motility in Serratia liquefaciens MG1. Microbiology 12:3237–32344Google Scholar
  32. Rasmussen TB, Bjarnsholt T, Skindersoe ME, Hentzer M, Kristoffersen P, Kote M, Nielsen J, Eberl L, Givskov M (2005) Screening for quorum-sensing inhibitors (QSI) by use of a novel genetic system, the QSI selector. J Bacteriol 187:1799–1814PubMedCrossRefPubMedCentralGoogle Scholar
  33. Riddle DL, Blumenthal T, Meyers BJ, Priess JR (1997) C. elegans II edition. Cold Spring Harbor Laboratory, New YorkGoogle Scholar
  34. Rudrappa T, Bais HP (2008) Curcumin a known phenolic from Curcuma longa attenuates the virulence of Pseudomonas aeruginosa PAO1 in whole plant and animal pathogenicity models. J Agric Food Chem 56:1955–1962. doi: 10.1021/jf072591j PubMedCrossRefGoogle Scholar
  35. Sarabhai S, Sharma P, Capalash N (2013) Ellagic acid derivatives from Terminalia chebula Retz. downregulate the expression of quorum sensing genes to attenuate Pseudomonas aeruginosa PAO1 virulence. PLoS One 8:e53441PubMedCrossRefPubMedCentralGoogle Scholar
  36. Senturk S, Ulusoy S, Bosgelmez-Tinaz G, Yagci A (2012) Quorum sensing and virulence of Pseudomonas aeruginosa during urinary tract infections. J Infect Dev Ctries 6:501–507. doi: 10.3855/jidc.2543 PubMedGoogle Scholar
  37. Sifri CD, Begun J, Ausubel FM, Calderwood SB (2003) Caenorhabditis elegans as a model host for Staphylococcus aureus pathogenesis. Infect Immun 71:2208–2219. doi: 10.1128/IAI.71.4.2208-2217.2003 PubMedCrossRefPubMedCentralGoogle Scholar
  38. Smith RS, Iglewski BH (2003) P. aeruginosa quorum-sensing systems and virulence. Curr Opin Microbiol 6:56–60. doi: 10.1016/S1369-5274(03)00008-0 PubMedCrossRefGoogle Scholar
  39. Smyth AR, Cifelli PM, Ortori CA, Righetti K, Lewis S, Erskine P, Holland ED, Givskov M, Williams P, Cámara M, Barrett DA, Knox A (2010) Garlic as an inhibitor of Pseudomonas aeruginosa quorum sensing in cystic fibrosis–a pilot randomized controlled trial. Pediatr Pulmonol 45:356–362. doi: 10.1002/ppul.21193 PubMedGoogle Scholar
  40. Sperandio V, Torres AG, Jarvis B, Nataro JP, Kaper JB (2003) Bacteria–host communication: the language of hormones. Proc Natl Acad Sci USA 100:8951–8956. doi: 10.1073/pnas.1537100100 PubMedCrossRefPubMedCentralGoogle Scholar
  41. Tan MW, Rahme LG, Sternberg JA, Tompkins RG, Ausuble FM (1999) Pseudomonas aeruginosa killing of Caenorhabditis elegans used to identify P. aeruginosa virulence factors. Proc Natl Acad Sci USA 96:2408–2413. doi: 10.1073/pnas.96.5.2408 PubMedCrossRefPubMedCentralGoogle Scholar
  42. Zaborin A, Romanowski K, Gerdes S, Holbrook C, Francios L, Jason L, Valeriy P, Diggle SP, Wike A, Righetti K, Morozova I, Babrowski T, Liu DC, Zaborina O, Alverdy JC (2009) Red death in Caenorhabditis elegans caused by Pseudomonas aeruginosa PAO1. Proc Natl Acad Sci USA 106:6327–6332. doi: 10.1073/pnas.0813199106 PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer India 2015

Authors and Affiliations

  1. 1.Department of MicrobiologyPanjab UniversityChandigarhIndia
  2. 2.Department of BiotechnologyPanjab UniversityChandigarhIndia

Personalised recommendations