Structural Basis for Native Agonist and Synthetic Inhibitor Recognition by the Pseudomonas aeruginosa Quorum Sensing Regulator PqsR (MvfR)

PLoS Pathogens

Volumn 9, Issue 7, 2013, Pages

  Ilangovan, Aravindan ^a,c   Fletcher, Matthew ^a   Rampioni, Giordano ^a,d   Pustelny, Christian ^a,e   Rumbaugh, Kendra ^b   Heeb, Stephan ^a   Cámara, Miguel ^a   Truman, Alex ^a   Chhabra, Siri Ram ^a   Emsley, Jonas ^a   Williams, Paul ^a  

^a UNIVERSITY OF NOTTINGHAM   (United Kingdom)

^b UNIVERSITY OF TEXAS   (United States)

^c UNIVERSITY OF LONDON   (United Kingdom)

^d ROMA TRE UNIVERSITY   (Italy)

^e HELMHOLTZ CENTRE FOR INFECTION RESEARCH   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ALKYLQUINOLONE; AMINO ACID; PSEUDOMONAS AERUGINOSA QUORUM SENSING REGULATOR; PYOCYANINE; QUINAZOLINONE DERIVATIVE; QUINOLONE; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG; VIRULENCE FACTOR;

ARTICLE; BINDING SITE; BIOFILM; BIOLUMINESCENCE; CONTROLLED STUDY; CRYSTAL STRUCTURE; CRYSTALLIZATION; GENE EXPRESSION; LIGAND BINDING; NONHUMAN; PROTEIN EXPRESSION; PROTEIN INTERACTION; PROTEIN PURIFICATION; PSEUDOMONAS AERUGINOSA; QUORUM SENSING; SITE DIRECTED MUTAGENESIS;

EID: 84883487578     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1003508     Document Type: Article

References (53)

1. Williams P, Winzer K, Chan WC, Camara M, (2007) Look who's talking: communication and quorum sensing in the bacterial world. Philos Trans R Soc Lond B Biol Sci 362: 1119-1134.
2. Clatworthy AE, Pierson E, Hung DT, (2007) Targeting virulence: a new paradigm for antimicrobial therapy. Nat Chem Biol 3: 541-548.
3. Williams P, (2002) Quorum sensing: an emerging target for antibacterial chemotherapy? Expert Opin Ther Targets 6: 257-274.
4. Kaufmann GF, Park J, Janda KD, (2008) Bacterial quorum sensing: a new target for anti-infective immunotherapy. Expert Opin Biol Ther 8: 719-724.
5. Déziel E, Lépine F, Milot S, He JX, Mindrinos MN, et al. (2004) Analysis of Pseudomonas aeruginosa 4-hydroxy-2-alkylquinolines (HAQs) reveals a role for 4-hydroxy-2-heptylquinoline in cell-to-cell communication. Proc Natl Acad Sci U S A 101: 1339-1344.
6. Diggle SP, Lumjiaktase P, Dipilato F, Winzer K, Kunakorn M, et al. (2006) Functional genetic analysis reveals a 2-alkyl-4-quinolone signaling system in the human pathogen Burkholderia pseudomallei and related bacteria. Chem Biol 13: 701-710.
7. Boucher HW, Talbot GH, Bradley JS, Edwards JE, Gilbert D, et al. (2009) Bad bugs, no drugs: No ESKAPE! An update from the Infectious Diseases Society of America. Clin Infect Dis 48: 1-12.
8. Williams P, Camara M, (2009) Quorum sensing and environmental adaptation in Pseudomonas aeruginosa: a tale of regulatory networks and multifunctional signal molecules. Curr Opin Microbiol 12: 182-191.
9. Heeb S, Fletcher MP, Chhabra SR, Diggle SP, Williams P, et al. (2011) Quinolones: from antibiotics to autoinducers. FEMS Microbiol Rev 35: 247-274.
10. Lépine F, Milot S, Déziel E, He J, Rahme LG, (2004) Electrospray/mass spectrometric identification and analysis of 4-hydroxy-2-alkylquinolines (HAQs) produced by Pseudomonas aeruginosa. Journal of the American Society for Mass Spectrometry 15: 862-869.
11. Ortori CA, Dubern JF, Chhabra SR, Camara M, Hardie K, et al. (2011) Simultaneous quantitative profiling of N-acyl-l-homoserine lactone and 2-alkyl-4(1H)-quinolone families of quorum-sensing signaling molecules using LC-MS/MS. Anal Bioanal Chem 399: 839-850.
12. Cao H, Krishnan G, Goumnerov B, Tsongalis J, Tompkins R, et al. (2001) A quorum sensing-associated virulence gene of Pseudomonas aeruginosa encodes a LysR-like transcription regulator with a unique self-regulatory mechanism. Proc Natl Acad Sci U S A 98: 14613-14618.
13. Gallagher LA, McKnight SL, Kuznetsova MS, Pesci EC, Manoil C, (2002) Functions required for extracellular quinolone signaling by Pseudomonas aeruginosa. J Bacteriol 184: 6472-6480.
14. Diggle SP, Matthijs S, Wright VJ, Fletcher MP, Chhabra SR, et al. (2007) The Pseudomonas aeruginosa 4-quinolone signal molecules HHQ and PQS play multifunctional roles in quorum sensing and iron entrapment. Chem Biol 14: 87-96.
15. Schertzer JW, Brown SA, Whiteley M, (2010) Oxygen levels rapidly modulate Pseudomonas aeruginosa social behaviours via substrate limitation of PqsH. Mol Microbiol 77: 1527-1538.
16. Rampioni G, Pustelny C, Fletcher MP, Wright VJ, Bruce M, et al. (2010) Transcriptomic analysis reveals a global alkyl-quinolone-independent regulatory role for PqsE in facilitating the environmental adaptation of Pseudomonas aeruginosa to plant and animal hosts. Environ Microbiol 12: 1659-1673.
17. Collier DN, Anderson L, McKnight SL, Noah TL, Knowles M, et al. (2002) A bacterial cell to cell signal in the lungs of cystic fibrosis patients. FEMS Microbiol Lett 215: 41-46.
18. Machan ZA, Taylor GW, Pitt TL, Cole PJ, Wilson R, (1992) 2-heptyl-4-hydroxyquinoline N-oxide, an antistaphylococcal agent produced by Pseudomonas aeruginosa. J Antimicrob Chemother 30: 615-623.
19. McGrath S, Wade DS, Pesci EC, (2004) Dueling quorum sensing systems in Pseudomonas aeruginosa control the production of the Pseudomonas quinolone signal (PQS). FEMS Microbiol Lett 230: 27-34.
20. Wade DS, Calfee MW, Rocha ER, Ling EA, Engstrom E, et al. (2005) Regulation of Pseudomonas quinolone signal synthesis in Pseudomonas aeruginosa. J Bacteriol 187: 4372-4380.
21. Xiao GP, Déziel E, He JX, Lépine F, Lesic B, et al. (2006) MvfR, a key Pseudomonas aeruginosa pathogenicity LTTR-class regulatory protein, has dual ligands. Mol Microbiol 62: 1689-1699.
22. Xiao GP, He JX, Rahme LG, (2006) Mutation analysis of the Pseudomonas aeruginosa mvfR and pqsABCDE gene promoters demonstrates complex quorum-sensing circuitry. Microbiology 152: 1679-1686.
23. Fletcher MP, Diggle SP, Crusz SA, Chhabra SR, Camara M, et al. (2007) A dual biosensor for 2-alkyl-4-quinolone quorum-sensing signal molecules. Environ Microbiol 9: 2683-2693.
24. Mashburn-Warren L, Howe J, Garidel P, Richter W, Steiniger F, et al. (2008) Interaction of quorum signals with outer membrane lipids: insights into prokaryotic membrane vesicle formation. Mol Microbiol 69: 491-502.
25. Pustelny C, Albers A, Buldt-Karentzopoulos K, Parschat K, Chhabra SR, et al. (2009) Dioxygenase-mediated quenching of quinolone-dependent quorum sensing in Pseudomonas aeruginosa. Chem Biol 16: 1259-1267.
26. Calfee MW, Coleman JP, Pesci EC, (2001) Interference with Pseudomonas quinolone signal synthesis inhibits virulence factor expression by Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 98: 11633-11637.
27. Lesic B, Lépine F, Déziel E, Zhang JW, Zhang QH, et al. (2007) Inhibitors of pathogen intercellular signals as selective anti-infective compounds. PLoS Pathog 3: 1229-1239.
28. Storz MP, Maurer CK, Zimmer C, Wagner N, Brengel C, et al. (2012) Validation of PqsD as an anti-biofilm target in Pseudomonas aeruginosa by development of small-molecule inhibitors. J Am Chem Soc 134: 16143-16146.
29. Maddocks SE, Oyston PCF, (2008) Structure and function of the LysR-type transcriptional regulator (LTTR) family proteins. Microbiology 154: 3609-3623.
30. Reen FJ, Barret M, Fargier E, O'Muinneachain M, O'Gara F, (2013) Molecular evolution of LysR-type transcriptional regulation in Pseudomonas aeruginosa. Mol Phylogenet Evol 66: 1041-1049.
31. Craven SH, Ezezika OC, Haddad S, Hall RA, Momany C, et al. (2009) Inducer responses of BenM, a LysR-type transcriptional regulator from Acinetobacter baylyi ADP1. Mol Microbiol 72: 881-894.
32. Monferrer D, Tralau T, Kertesz MA, Dix I, Sola M, et al. (2010) Structural studies on the full-length LysR-type regulator TsaR from Comamonas testosteroni T-2 reveal a novel open conformation of the tetrameric LTTR fold. Mol Microbiol 75: 1199-1214.
33. Kefala K, Kotsifaki D, Providaki M, Kapetaniou EG, Rahme L, et al. (2012) Purification, crystallization and preliminary X-ray diffraction analysis of the C-terminal fragment of the MvfR protein from Pseudomonas aeruginosa. Acta Crystallogr F Struct Biol Cryst Commun 68: 695-697.
34. Xu N, Yu S, Moniot S, Weyand M, Blankenfeldt W, (2012) Crystallization and preliminary crystal structure analysis of the ligand-binding domain of PqsR (MvfR), the Pseudomonas quinolone signal (PQS) responsive quorum-sensing transcription factor of Pseudomonas aeruginosa. Acta Crystallogr F Struct Biol Cryst Commun 68: 1034-1039.
35. Ezezika OC, Haddad S, Clark TJ, Neidle EL, Momany C, (2007) Distinct effector-binding sites enable synergistic transcriptional activation by BenM, a LysR-type regulator. J Mol Biol 367: 616-629.
36. Ruangprasert A, Craven SH, Neidle EL, Momany C, (2010) Full-length structures of BenM and two variants reveal different oligomerization schemes for LysR-type transcriptional regulators. J Mol Biol 404: 568-586.
37. Diggle SP, Cornelis P, Williams P, Cámara M, (2006) 4-quinolone signalling in Pseudomonas aeruginosa: old molecules, new perspectives. Int J Med Microbiol 296: 83-91.
38. Mavrodi DV, Bonsall RF, Delaney SM, Soule MJ, Phillips G, et al. (2001) Functional analysis of genes for biosynthesis of pyocyanin and phenazine-1-carboxamide from Pseudomonas aeruginosa PAO1. J Bacteriol 183: 6454-6465.
39. Allesen-Holm M, Barken KB, Yang L, Klausen M, Webb JS, et al. (2006) A characterization of DNA release in Pseudomonas aeruginosa cultures and biofilms. Mol Microbiol 59: 1114-1128.
40. Diggle SP, Winzer K, Chhabra SR, Chhabra SR, Worrall KE, et al. (2003) The Pseudomonas aeruginosa quinolone signal molecule overcomes the cell density-dependency of the quorum sensing hierarchy, regulates rhl-dependent genes at the onset of stationary phase and can be produced in the absence of LasR. Mol Microbiol 50: 29-43.
41. Choi HJ, Kim SJ, Mukhopadhyay P, Cho S, Woo JR, et al. (2001) Structural basis of the redox switch in the OxyR transcription factor. Cell 105: 103-113.
42. van Keulen G, Girbal L, van den Bergh ERE, Dijkhuizen L, Meijer WG, (1998) The LysR-type transcriptional regulator CbbR controlling autotrophic CO2 fixation by Xanthobacter flavus is an NADPH sensor. J Bacteriol 180: 1411-1417.
43. Hodgkinson J, Bowden SD, Galloway WRJD, Spring DR, Welch M, (2010) Structure-activity analysis of the Pseudomonas quinolone signal molecule. J Bacteriol 192: 3833-3837.
44. Klein T, Henn C, de Jong JC, Zimmer C, Kirsch B, et al. (2012) Identification of small-molecule antagonists of the Pseudomonas aeruginosa transcriptional regulator PqsR: biophysically guided hit discovery and optimization. ACS Chem Biol 7: 1496-1501.
45. Lu CB, Kirsch B, Zimmer C, de Jong JC, Henn C, et al. (2012) Discovery of antagonists of PqsR, a key player in 2-alkyl-4-quinolone-dependent quorum sensing in Pseudomonas aeruginosa. Chem Biol 19: 381-390.
46. Zaborina O, Lépine F, Xiao G, Valuckaite V, Chen Y, et al. (2007) Dynorphin activates quorum sensing quinolone signaling in Pseudomonas aeruginosa. PLoS Pathog 3: e35.
47. Chen J, Xie JP, (2011) Role and regulation of bacterial LuxR-like regulators. J Cell Biochem 112: 2694-2702.
48. Ombaka EA, Cozens RM, Brown MRW, (1983) Influence of nutrient limitation of growth on stability and production of virulence factors of mucoid and nonmucoid strains of Pseudomonas aeruginosa. Rev Infect Dis 5: S880-S888.
49. Milton DL, OToole R, Horstedt P, WolfWatz H, (1996) Flagellin A is essential for the virulence of Vibrio anguillarum. J Bacteriol 178: 1310-1319.
50. Westfall LW, Luna AM, San Francisco M, Diggle SP, Worrall KE, et al. (2004) The Pseudomonas aeruginosa global regulator MvaT specifically binds to the ptxS upstream region and enhances ptxS expression. Microbiology 150: 3797-3806.
51. Heeb S, Blumer C, Haas D, (2002) Regulatory RNA as mediator in GacA/RsmA-dependent global control of exoproduct formation in Pseudomonas fluorescens CHA0. J Bacteriol 184: 1046-1056.
52. Horton RM, Hunt HD, Ho SN, Pullen JK, Pease LR, (1989) Engineering hybrid genes without the use of restriction enzymes- gene-splicing by overlap extension. Gene 77: 61-68.
53. Benoit MR, Conant CG, Ionescu-Zanetti C, Schwartz M, Matin A, (2010) New device for high-throughput viability screening of flow biofilms. Appl Environ Microbiol 76: 4136-4142.