미생물학회지 (Korean Journal of Microbiology)

  • 제44권2호
  • /
  • Pages.85-92
  • /
  • 2008
  • /
  • 0440-2413(pISSN)
  • /
  • 2383-9902(eISSN)
한국미생물학회 (The Microbiological Society of Korea)
권호 표지

Minority report; Pseudomonas aeruginosa의 정족수 인식(쿼럼 센싱) 신호물질로써의 Diketopiperazines과 Pyocyanin

Minority report; Diketopiperazines and Pyocyanin as Quorum Sensing Signals in Pseudomonas aeruginosa

  • 이준희 (부산대학교 약학대학 약학과)
  • Lee, Joon-Hee (Department of Pharmacy, College of Pharmacy, Pusan National University)
  • 발행 : 2008.06.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Pseudomonas aeruginosa는 기회 감염성 병원균으로, Cystic fibrosis, 미생물 감염성 각막염,화상 부위 2차 감염 등의 다양한 질병을 초래한다. 정족수 인식(쿼럼 센싱)이라고도 알려져 있는 세포간 신호전달 기전이 이러한 감염에서 중요한 역할을 하기 때문에 P. aeruginosa의 정족수 인식 시스템들이 집중적으로 연구되어 왔다. P. aeruginosa의 정족수 인식 시스템들을 소개하는 많은 문헌들이 주로 두 개의 주요 acyl-homoserine lactone (AHL) 계열 정족수 신호물질들인 N-3-oxododecanoyl homoserine lactone (3OC12)과 N-butanoyl homoserine lactone (C4)에 초점을 맞추어 설명하고 있지만, 실제로는 몇 가지 새로운 신호물질들이 발견되어져 왔고, 그들이 P. aeruginosa의 병독성과 신호전달에 중요한 역할을 할 수 있음이 제안되어져 왔다. 그 중 하나가 PQS(Pseudomonas quinolone signal; 2-heptyl-3-hydroxy-4-quinolone)인데, 이 물질은 현재 P. aeruginosa의 잘 규명된 주요 신호물질로 인식되고 있다. 이에 더하여, 최근의 연구들은 또 다른 가능성 있는 P. aeruginosa신호물질들을 제안해 왔는데, diketopiperazines (DKPs)과 pyocyanin이 그들이다. DKPs는 환형 dipeptide로써 이를 구성하는 아미노산의 종류에 따라 다양한 구조를 가진다. P. aeruginosa의 배양액에서 검출된 몇몇 DKPs들이 기존에는 AHL에만 특이적으로 반응한다고 알려졌던 Vibrio 랸�N갸 LuxR biosensor를 활성화 시킬 수 있다는 것이 발견되어 새로운 신호물질로 제안되었다. Pyocyanin (1-hydroxy-5-methyl-phenazine)은 P. aeruginosa가 생산하는 여러 phenazine 화합물들 중의 하나로써, 특징적인 청록색을 띄는 산화-환원 활성물질이다. 이 물질도 정체 성장기 동안 일부 정족수 인식의 조절을 받는 유전자들의 발현을 증가시키는 최종 신호 인자로 최근 제안되었으며, 그 신호는 또 다른 전사 조절 인자인 SoxR에 의해 매개된다고 제안되었다. 본 논문에서는 P. aeruginosa에서 새롭게 발견, 제안되고 있는 이들 신호 전달 물질들에 대해 자세히 다루어 보기로 한다.

Pseudomonas aeruginosa is an opportunistic human pathogen, causing a wide variety of infections including cystic fibrosis, microbial keratitis, and burn wound infections. The cell-to-cell signaling mechanism known as quorum sensing (QS) plays a key role in these infections and the QS systems of P. aeruginosa have been most intensively studied. While many literatures that introduce the QS systems of P. aeruginosa have mostly focused on two major acyl-homo serine lactone (acyl-HSL) QS signals, N-3-oxododecanoyl homoserine lactone (3OC12) and N-butanoyl homoserine lactone (C4), several new signal molecules have been discovered and suggested for their significant roles in signaling and virulence of P. aeruginosa. One of them is PQS (Pseudomonas quinolone signal; 2-heptyl-3-hydroxy-4-quinolone), which is now considered as a well-characterized major signal meolecule of P. aeruginosa. In addition, recent researches have also suggested some more putative signal molecules of P. aeruginosa, which are diketopiperazines (DKPs) and pyocyanin. DKPs are cyclic dipeptides and structurally diverse depending on what amino acids are involved in composition. Some DKPs from the culture supernatant of P. aeruginosa are suggested as new diffusible signal molecules, based on their ability to activate Vibrio fischeri LuxR biosensors that are previously considered specific for acyl-HSLs. Pyocyanin (1-hydroxy-5-methyl-phenazine), one of phenazine derivatives produced by P. aeruginosa is a characteristic blue-green pigment and redox-active compound. This has been recently suggested as a terminal signaling factor to upregulate some QS-controlled genes during stationary phase under the mediation of a transcription factor, SoxR. Here, details about these newly emerging signaling molecules of P. aeruginosa are discussed.

키워드

참고문헌

  1. Adamczeski, M., A.R. Reed, and P. Crews. 1995. New and known diketopiperazines from the Caribbean sponge, Calyx cf. podatypa. J. Nat. Prod. 58, 201-208 https://doi.org/10.1021/np50116a007
  2. Brelles-Marino, G. and E.J. Bedmar. 2001. Detection, purification and characterisation of quorum-sensing signal molecules in plant-associated bacteria. J. Biotechnol. 91, 197-209 https://doi.org/10.1016/S0168-1656(01)00330-3
  3. Degrassi, G., C. Aguilar, M. Bosco, S. Zahariev, S. Pongor, and V. Venturi. 2002. Plant growth-promoting Pseudomonas putida WCS358 produces and secretes four cyclic dipeptides: cross-talk with quorum sensing bacterial sensors. Curt. Microbiol. 45, 250-254 https://doi.org/10.1007/s00284-002-3704-y
  4. Deziel, E., S. Gopalan, A.P. Tampakaki, F. Lepine, K.E. Padfield, M. Saucier, G. Xiao, and L.G. Rahme. 2005. The contribution of MvfR to Pseudomonas aeruginosa pathogenesis and quorum sensing circuitry regulation: multiple quorum sensing-regulated genes are modulated without affecting lasRI, rhlRI or the production of N-acyl-L-homoserine lactones. Mol. Microbiol. 55, 998-1014 https://doi.org/10.1111/j.1365-2958.2004.04448.x
  5. Dietrich, L.E., A. Price-Whelan, A. Petersen, M. Whiteley, and D.K. Newman. 2006. The phenazine pyocyanin is a terminal signalling factor in the quorum sensing network of Pseudomonas aeruginosa. Mol. Microbiol. 61, 1308-1321 https://doi.org/10.1111/j.1365-2958.2006.05306.x
  6. Diggle, S.P., P. Cornelis, P. Williams, and M. Camara. 2006. 4-quinolone signalling in Pseudomonas aeruginosa: old molecules, new perspectives. Int. J. Med. Microbiol. 296, 83-91 https://doi.org/10.1016/j.ijmm.2006.01.038
  7. Farrow, J.M., 3rd and E.C. Pesci. 2007. Two distinct pathways supply anthranilate as a precursor of the Pseudomonas quinolone signal. J. Bacteriol. 189, 3425-3433 https://doi.org/10.1128/JB.00209-07
  8. Gallagher, L.A., S.L. McKnight, M.S. Kuznetsova, E.C. Pesci, and C. Manoil. 2002. Functions required for extracellular quinolone signaling by Pseudomonas aeruginosa. J. Bacteriol. 184, 6472-6480 https://doi.org/10.1128/JB.184.23.6472-6480.2002
  9. Gaudu, P., S. Dubrac, and D. Touati. 2000. Activation of SoxR by overproduction of desulfoferrodoxin: multiple ways to induce the soxRS regulon. J. Bacteriol. 182, 1761-1763 https://doi.org/10.1128/JB.182.6.1761-1763.2000
  10. Hassett, D.J., L. Charniga, K. Bean, D.E. Ohman, and M.S. Cohen. 1992. Response of Pseudomonas aeruginosa to pyocyanin: mechanisms of resistance, antioxidant defenses, and demonstration of a manganese-cofactored superoxide dismutase. Infect. Immun. 60, 328-336
  11. Hedner, E., M. Sjogren, S. Hodzic, R. Andersson, U. Goransson, P.R. Jonsson, and L. Bohlin. 2008. Antifouling activity of a dibrominated cyclopeptide from the marine sponge Geodia barretti. J. Nat. Prod. 71, 330-333 https://doi.org/10.1021/np0705209
  12. Henke, J.M. and B.L. Bassler. 2004. Bacterial social engagements. Trends Cell. Biol. 14, 648-656 https://doi.org/10.1016/j.tcb.2004.09.012
  13. Hentschel, U., K.M. Usher, and M.W. Taylor. 2006. Marine sponges as microbial fermenters. FEMS Microbiol. Ecol. 55, 167-177 https://doi.org/10.1111/j.1574-6941.2005.00046.x
  14. Holden, I., I. Swift, and I. Williams. 2000. New signal molecules on the quorum-sensing block. Trends Microbiol. 8, 101-104;discussion 103-4 https://doi.org/10.1016/S0966-842X(00)01718-2
  15. Holden, M.T., S. Ram Chhabra, R. De Nys, P. Stead, N.J. Bainton, P.J. Hill, M. Manefield, N. Kumar, M. Labatte, D. England, S. Rice, M. Givskov, G.P. Salmond, G.S. Stewart, B.W. Bycroft, S. Kjelleberg, and P. Williams. 1999. Quorum-sensing cross talk: isolation and chemical characterization of cyclic dipeptides from Pseudomonas aeruginosa and other Gram-negative bacteria. Mol. Microbiol. 33, 1254-1266 https://doi.org/10.1046/j.1365-2958.1999.01577.x
  16. Jayatilake, G.S., M.P. Thornton, A.C. Leonard, J.E. Grimwade, and B.J. Baker. 1996. Metabolites from an Antarctic sponge-associated bacterium, Pseudomonas aeruginosa. J. Nat. Prod. 59, 293-296 https://doi.org/10.1021/np960095b
  17. Kendall, M.M. and V. Sperandio. 2007. Quorum sensing by enteric pathogens. Curr. Opin. Gastroenterol. 23, 10-15 https://doi.org/10.1097/MOG.0b013e3280118289
  18. Kobayashi, K. and S. Tagawa. 2004. Activation of SoxR-dependent transcription in Pseudomonas aeruginosa. J. Biochem. 136, 607-615 https://doi.org/10.1093/jb/mvh168
  19. Kohanski, M.A., D.J. Dwyer, B. Hayete, C.A. Lawrence, and J.J. Collins. 2007. A common mechanism of cellular death induced by bactericidal antibiotics. Cell 130, 797-810 https://doi.org/10.1016/j.cell.2007.06.049
  20. Lautru, S., M. Gondry, R. Genet, and J.L. Pernodet. 2002. The albonoursin gene Cluster of S. noursei biosynthesis of diketopiperazine metabolites independent of nonribosomal peptide synthetases. Chem. Biol. 9, 1355-1364 https://doi.org/10.1016/S1074-5521(02)00285-5
  21. Liochev, S.I. and I. Fridovich. 1992. Fumarase C, the stable fumarase of Escherichia coli, is controlled by the soxRS regulon. Proc. Natl. Acad. Sci. USA 89, 5892-5896
  22. Liochev, S.I., A. Hausladen, W.F. Beyer, Jr., and I. Fridovich. 1994. NADPH: ferredoxin oxidoreductase acts as a paraquat diaphorase and is a member of the soxRS regulon. Proc. Natl. Acad. Sci. USA 91, 1328-1331
  23. Martins, M.B. and I. Carvalho. 2007. Diketopiperazines: biological activity and synthesis. Tetrahedron 63, 9923-9932 https://doi.org/10.1016/j.tet.2007.04.105
  24. Mohamed, N.M., E.M. Cicirelli, J. Kan, F. Chen, C. Fuqua, and R.T. Hill. 2008. Diversity and quorum-sensing signal production of Proteobacteria associated with marine sponges. Environ. Microbiol. 10, 75-86
  25. Oglesby, A.G, J.M. Farrow, 3rd, J.H. Lee, A.P. Tomaras, E.P. Greenberg, E.C. Pesci, and M.L. Vasil. 2008. The influence of iron on Pseudomonas aeruginosa physiology: a regulatory link between iron and quorum sensing. J. Biol. Chem. Article in Press
  26. Palma, M., J. Zurita, J.A. Ferreras, S. Worgall, D.H. Larone, L. Shi, F. Campagne, and L.E. Quadri. 2005. Pseudomonas aeruginosa SoxR does not conform to the archetypal paradigm for SoxR-dependent regulation of the bacterial oxidative stress adaptive response. Infect. Immun. 73, 2958-2966 https://doi.org/10.1128/IAI.73.5.2958-2966.2005
  27. Park, D.K., K.E. Lee, C.H. Baek, I.H. Kim, J.H. Kwon, W.K. Lee, K.H. Lee, B.S. Kim, S.H. Choi, and K.S. Kim. 2006. Cyclo(Phe-Pro) modulates the expression of ompU in Vibrio spp. J. Bacteriol. 188, 2214-2221 https://doi.org/10.1128/JB.188.6.2214-2221.2006
  28. Park, W., S. Pena-Llopis, Y. Lee, and B. Demple. 2006. Regulation of superoxide stress in Pseudomonas putida KT2440 is different from the SoxR paradigm in Escherichia coli. Biochem. Biophys. Res. Commun. 341, 51-56 https://doi.org/10.1016/j.bbrc.2005.12.142
  29. Parsek, M.R. and E.P. Greenberg. 2005. Sociomicrobiology: the connections between quorum sensing and biofilms. Trends Microbiol. 13, 27-33 https://doi.org/10.1016/j.tim.2004.11.007
  30. Pesci, E.C. 2000. New signal molecules on the quorum-sensing block: response. Trends Microbiol. 8, 103-104 https://doi.org/10.1016/S0966-842X(00)01717-0
  31. Pomposiello, P.J. and B. Demple. 2001. Redox-operated genetic switches: the SoxR and OxyR transcription factors. Trends Biotechnol. 19, 109-114 https://doi.org/10.1016/S0167-7799(00)01542-0
  32. Price-Whelan, A., L.E. Dietrich, and D.K. Newman. 2007. Pyocyanin alters redox homeostasis and carbon flux through central metabolic pathways in Pseudomonas aeruginosa PA14. J. Bacteriol. 189, 6372-6381 https://doi.org/10.1128/JB.00505-07
  33. Privalle, C.T., S.E. Kong, and I. Fridovich. 1993. Induction of manganese-containing superoxide dismutase in anaerobic Escherichia coli by diamide and 1,1O-phenanthroline: sites of transcriptional regulation. Proc. Natl. Acad. Sci. USA 90, 2310-2314
  34. Rahme, L.G., E.J. Stevens, S.F. Wolfort, J. Shao, R.G. Tompkins, and F.M. Ausubel. 1995. Common virulence factors for bacterial pathogenicity in plants and animals. Science 268, 1899-1902 https://doi.org/10.1126/science.7604262
  35. Reading, N.C. and V. Sperandio. 2006. Quorum sensing: the many languages of bacteria. FEMS Microbiol. Lett. 254, 1-11 https://doi.org/10.1111/j.1574-6968.2005.00001.x
  36. Schuster, M. and E.P. Greenberg. 2006. A network of networks: quorum-sensing gene regulation in Pseudomonas aeruginosa. Int. J. Med. Microbiol. 296, 73-81 https://doi.org/10.1016/j.ijmm.2006.01.036
  37. Schuster, M., C.P. Lostroh, T. Ogi, and E.P. Greenberg. 2003. Identification, timing, and signal specificity of Pseudomonas aeruginosa quorum-controlled genes: a transcriptome analysis. J. Bacteriol. 185, 2066-2079 https://doi.org/10.1128/JB.185.7.2066-2079.2003
  38. Sjogren, M., U. Goransson, A.L. Johnson, M. Dahlstrom, R. Andersson, J. Bergman, P.R. Jonsson, and L. Bohlin. 2004. Antifouling activity of brominated cyclopeptides from the marine sponge Geodia barretti. J. Nat. Prod. 67, 368-372 https://doi.org/10.1021/np0302403
  39. Stierle, A.C., J.H. Cardellina, and G.A. Strobel. 1988. Maculosin, a host-specific phytotoxin for spotted knapweed from Alternaria alternata. Proc. Natl. Acad. Sci. USA 85, 8008-8011
  40. Taylor, M.W., P.J. Schupp, H.J. Baillie, T.S. Charlton, R. De Nys, S. Kjelleberg, and P.D. Steinberg. 2004. Evidence for acyl homoserine lactone signal production in bacteria associated with marine sponges. Appl. Environ. Microbiol. 70, 4387-4389 https://doi.org/10.1128/AEM.70.7.4387-4389.2004
  41. Urata, M., M. Miyakoshi, S. Kai, K. Maeda, H. Habe, T. Omori, H. Yamane, and H. Nojiri. 2004. Transcriptional regulation of the ant operon, encoding two-component anthranilate 1,2-dioxygenase, on the carbazole-degradative plasmid pCAR1 of Pseudomonas resinovorans strain CA10. J. Bacteriol. 186, 6815-6823 https://doi.org/10.1128/JB.186.20.6815-6823.2004
  42. Welch, M., H. Mikkelsen, J.E. Swatton, D. Smith, G.L. Thomas, F.G. Glansdorp, and D.R. Spring. 2005. Cell-cell communication in Gram-negative bacteria. Mol. Biosyst. 1, 196-202 https://doi.org/10.1039/b505796p
  43. Williams, P. 2007. Quorum sensing, communication and crosskingdom signalling in the bacterial world. Microbiology 153, 3923-3938 https://doi.org/10.1099/mic.0.2007/012856-0
  44. Wilson, R., T. Pitt, G. Taylor, D. Watson, J. MacDermot, D. Sykes, D. Roberts, and P. Cole. 1987. Pyocyanin and 1-hydroxyphenazine produced by Pseudomonas aeruginosa inhibit the beating of human respiratory cilia in vitro. J. Clin. Invest 79, 221-229 https://doi.org/10.1172/JCI112787