Chapter 14 : Quorum Sensing in the Gastrointestinal Tract

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This chapter reviews the published literature concerning quorum sensing (QS) among bacteria of the gastrointestinal (GI) tract, with particular emphasis on pathogenic species that cause infection in the GI tract. Three major QS circuits have been described: one used primarily by gram-negative bacteria, one used primarily by gram-positive bacteria, and one that is universal. The gram-negative bacterial QS system involves the use of acyl homoserine lactones (AHLs) as autoinducers, which then bind to response regulators that affect gene expression. The first evidence that QS could be involved in the regulation of virulence factors of GI pathogens was found with enteropathogenic (EPEC), which causes nonbloody diarrhea primarily in infants in developing countries, and enterohemorrhagic (EHEC), which causes bloody diarrhea and hemolytic-uremic syndrome. The major virulence factors for are cholera toxin (CT) and the toxin-coregulated pilus (TCP), both of which are regulated as part of the ToxR regulon. The discovery of QS in human pathogens has led to considerable interest in developing new therapeutic interventions to interfere with the signaling molecules. There are at least three major strategies for the development of drugs that interrupt bacterial QS: (i) inhibition of QS signal synthesis, (ii) destruction or degradation of the signal, and (iii) inhibition of signal reception. A fundamental property of QS is that the greater the density of bacteria, the greater the density of signaling molecules and the greater the opportunity for cell-to-cell communication.

Citation: Kaper J, Prichett C, Michalski J. 2005. Quorum Sensing in the Gastrointestinal Tract, p 187-198. In Nataro J, Cohen P, Mobley H, Weiser J (ed), Colonization of Mucosal Surfaces. ASM Press, Washington, DC. doi: 10.1128/9781555817619.ch14
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1. Ahmer, B. M. 2004. Cell-to-cell signalling in Escherichia coli and Salmonella enterica. Mol. Microbiol. 52: 933 945.
2. Ahmer, B. M.,, J. van Reeuwijk,, C. D. Timmers,, P. J. Valentine,, and F. Heffron. 1998. Salmonella typhimurium encodes an SdiA homolog, a putative quorum sensor of the LuxR family, that regulates genes on the virulence plasmid. J. Bacteriol. 180: 1185 1193.
3. Atkinson, S.,, J. P. Throup,, G. S. Stewart,, and P. Williams. 1999. A hierarchical quorum-sensing system in Yersinia pseudotuberculosis is involved in the regulation of motility and clumping. Mol. Microbiol. 33: 1267 1277.
4. Bassler, B. L. 2002. Small talk. Cell-to-cell communication in bacteria. Cell 109: 421 424.
5. Berg, R. D. 1996. The indigenous gastrointestinal microflora. Trends Microbiol. 4: 430 435.
6. Borriello, S. P., 2002. The normal flora of the gastrointestinal tract, p. 1 24. In A. L. Hart,, A. J. Stagg,, H. Graffner,, H. Glise,, P. G. Falk,, and M. A. Kamm (ed.), Gut Ecology. Martin Dunitz, Ltd., London, United Kingdom.
7. Camara, M.,, P. Williams,, and A. Hardman. 2002. Controlling infection by tuning in and turning down the volume of bacterial small-talk. Lancet Infect. Dis. 2: 667 676.
8. Chen, X.,, S. Schauder,, N. Potier,, A. Van Dorsselaer,, I. Pelczer,, B. L. Bassler,, and F. M. Hughson. 2002. Structural identification of a bacterial quorum-sensing signal containing boron. Nature 415: 545 549.
9. Chun, C. K.,, E. A. Ozer,, M. J. Welsh,, J. Zabner,, and E. P. Greenberg. 2004. Inactivation of a Pseudomonas aeruginosa quorum-sensing signal by human airway epithelia. Proc. Natl. Acad. Sci. USA 101: 3587 3590.
10. Coburn, P. S.,, and M. S. Gilmore. 2003. The Enterococcus faecalis cytolysin: a novel toxin active against eukaryotic and prokaryotic cells. Cell. Microbiol. 5: 661 669.
11. Day, A. M.,, J. H. Cove,, and M. K. Phillips-Jones. 2003. Cytolysin gene expression in Enterococcus faecalis is regulated in response to aerobiosis conditions. Mol. Genet. Genomics 269: 31 39.
12. Day, W. A., Jr.,, and A. T. Maurelli. 2001. Shigella flexneri LuxS quorum-sensing system modulates virB expression but is not essential for virulence. Infect. Immun. 69: 15 23.
13. De Kievit, T. R.,, R. Gillis,, S. Marx,, C. Brown,, and B. H. Iglewski. 2001. Quorum-sensing genes in Pseudomonas aeruginosa biofilms: their role and expression patterns. Appl. Environ. Microbiol. 67: 1865 1873.
14. Dong, Y. H.,, J. L. Xu,, X. Z. Li,, and L. H. Zhang. 2000. AiiA, an enzyme that inactivates the acylhomoserine lactone quorum- sensing signal and attenuates the virulence of Erwinia carotovora. Proc. Natl. Acad. Sci. USA 97: 3526 3531.
15. Duan, K.,, C. Dammel,, J. Stein,, H. Rabin,, and M. G. Surette. 2003. Modulation of Pseudomonas aeruginosa gene expression by host microflora through interspecies communication. Mol. Microbiol. 50: 1477 1491.
16.. Elvers, K. T.,, and S. F. Park. 2002. Quorum sensing in Campylobacter jejuni: detection of a luxS encoded signalling molecule. Microbiology 148: 1475 1481.
17. Erickson, D. L.,, V. L. Nsereko,, D. P. Morgavi,, L. B. Selinger,, L. M. Rode,, and K. A. Beauchemin. 2002. Evidence of quorum sensing in the rumen ecosystem: detection of N-acyl homoserine lactone autoinducers in ruminal contents. Can. J. Microbiol. 48: 374 378.
18. Falcao, J. P.,, F. Sharp,, and V. Sperandio. 2004. Cell-to-cell signaling in intestinal pathogens. Curr. Issues Intest. Microbiol. 5: 9 17.
19. Fuqua, C.,, and E. P. Greenberg. 2002. Listening in on bacteria: acyl-homoserine lactone signalling. Nat. Rev. Mol. Cell Biol. 3: 685 695.
20. Fuqua, C.,, M. R. Parsek,, and E. P. Greenberg. 2001. Regulation of gene expression by cell-to-cell communication: acylhomoserine lactone quorum sensing. Annu. Rev. Genet. 35: 439 468.
21. Haas, W.,, B. D. Shepard,, and M. S. Gilmore. 2002. Twocomponent regulator of Enterococcus faecalis cytolysin responds to quorum-sensing autoinduction. Nature 415: 84 87.
22. Hammer, B. K.,, and B. L. Bassler. 2003. Quorum sensing controls biofilm formation in Vibrio cholerae. Mol. Microbiol. 50: 101 104.
23. Henke, J. M.,, and B. L. Bassler. 2004. Quorum sensing regulates type III secretion in Vibrio harveyi and Vibrio parahaemolyticus. J. Bacteriol. 186: 3794 3805.
24. Hentzer, M.,, and M. Givskov. 2003. Pharmacological inhibition of quorum sensing for the treatment of chronic bacterial infections. J. Clin. Investig. 112: 1300 1307.
25. Hentzer, M.,, H. Wu,, J. B. Andersen,, K. Riedel,, T. B. Rasmussen,, N. Bagge,, N. Kumar,, M. A. Schembri,, Z. Song,, P. Kristoffersen,, M. Manefield,, J. W. Costerton,, S. Molin,, L. Eberl,, P. Steinberg,, S. Kjelleberg,, N. Hoiby,, and M. Givskov. 2003. Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors. EMBOJ. 22: 3803 3815.
26. Jeon, B.,, K. Itoh,, N. Misawa,, and S. Ryu. 2003. Effects of quorum sensing on flaA transcription and autoagglutination in Campylobacter jejuni. Microbiol. Immunol. 47: 833 839.
27. Kanamaru, K.,, I. Tatsuno,, T. Tobe,, and C. Sasakawa. 2000. SdiA, an Escherichia coli homologue of quorum-sensing regulators, controls the expression of virulence factors in enterohaemorrhagic Escherichia coli O157:H7. Mol. Microbiol. 38: 805 816.
28. Kaper, J. B.,, and A. D. O’Brien (ed.). 1998. Escherichia coli and Other Shiga-Toxin Producing E. coli Strains. ASM Press, Washington, D.C.
29. Kim, S. Y.,, S. E. Lee,, Y. R. Kim,, C. M. Kim,, P. Y. Ryu,, H. E. Choy,, S. S. Chung,, and J. H. Rhee. 2003. Regulation of Vibrio vulnificus virulence by the LuxS quorum-sensing system. Mol. Microbiol. 48: 1647 1664.
30. Kovacikova, G.,, and K. Skorupski. 2002. Regulation of virulence gene expression in Vibrio cholerae by quorum sensing: HapR functions at the aphA promoter. Mol. Microbiol. 46: 1135 1147.
31. Macfarlane, G. T.,, and S. Macfarlane. 1997. Human colonic microbiota: ecology, physiology and metabolic potential of intestinal bacteria. Scand. J. Gastroenterol. Suppl. 222: 3 9.
32. Manefield, M.,, M. Welch,, M. Givskov,, G. P. Salmond,, and S. Kjelleberg. 2001. Halogenated furanones from the red alga, Delisea pulchra, inhibit carbapenem antibiotic synthesis and exoenzyme virulence factor production in the phytopathogen Erwinia carotovora. FEMS Microbiol. Lett. 205: 131 138.
33. Manna, A. C.,, and A. L. Cheung. 2003. sarU, a sarA homolog, is repressed by SarT and regulates virulence genes in Staphylococcus aureus. Infect. Immun. 71: 343 353.
34. Mayville, P.,, G. Ji,, R. Beavis,, H. Yang,, M. Goger,, R. P. Novick,, and T. W. Muir. 1999. Structure-activity analysis of synthetic autoinducing thiolactone peptides from Staphylococcus aureus responsible for virulence. Proc. Natl. Acad. Sci. USA 96: 1218 1223.
35. McCracken, V. J.,, and R. G. Lorenz. 2001. The gastrointestinal ecosystem: a precarious alliance among epithelium, immunity and microbiota. Cell. Microbiol. 3: 1 11.
36. McDaniel, T. K.,, K. G. Jarvis,, M. S. Donnenberg,, and J. B. Kaper. 1995. A genetic locus of enterocyte effacement conserved among diverse enterobacterial pathogens. Proc. Natl. Acad. Sci. USA 92: 1664 1668.
37. Michael, B.,, J. N. Smith,, S. Swift,, F. Heffron,, and B. M. Ahmer. 2001. SdiA of Salmonella enterica is a LuxR homolog that detects mixed microbial communities. J. Bacteriol. 183: 5733 5742.
38. Miller, M. B.,, K. Skorupski,, D. H. Lenz,, R. K. Taylor,, and B. L. Bassler. 2002. Parallel quorum sensing systems converge to regulate virulence in Vibrio cholerae. Cell 110: 303 314.
39. Mitsumori, M.,, L. Xu,, H. Kajikawa,, M. Kurihara,, K. Tajima,, J. Hai,, and A. Takenaka. 2003. Possible quorum sensing in the rumen microbial community: detection of quorum-sensing signal molecules from rumen bacteria. FEMS Microbiol. Lett. 219: 47 52.
40. Novick, R. P. 2003. Autoinduction and signal transduction in the regulation of staphylococcal virulence. Mol. Microbiol. 48: 1429 1449.
41. Ohtani, K.,, H. Hayashi,, and T. Shimizu. 2002. The luxS gene is involved in cell-cell signalling for toxin production in Clostridium perfringens. Mol. Microbiol. 44: 171 179.
42. Ozaki, E.,, H. Kato,, H. Kita,, T. Karasawa,, T. Maegawa,, Y. Koino,, K. Matsumoto,, T. Takada,, K. Nomoto,, R. Tanaka,, and S. Nakamura. 2004. Clostridium difficile colonization in healthy adults: transient colonization and correlation with enterococcal colonization. J. Med. Microbiol. 53: 167 172.
43. Parsek, M. R.,, and E. P. Greenberg. 2000. Acyl-homoserine lactone quorum sensing in gram-negative bacteria: a signaling mechanism involved in associations with higher organisms. Proc. Natl. Acad. Sci. USA 97: 8789 8793.
44. Parsek, M. R.,, D. L. Val,, B. L. Hanzelka,, J. E. Cronan, Jr.,, and E. P. Greenberg. 1999. Acyl homoserine-lactone quorumsensing signal generation. Proc. Natl. Acad. Sci. USA 96: 4360 4365.
45. Qin, X.,, K. V. Singh,, G. M. Weinstock,, and B. E. Murray. 2000. Effects of Enterococcus faecalis fsr genes on production of gelatinase and a serine protease and virulence. Infect. Immun. 68: 2579 2586.
46. Ruiz-Perez, F.,, J. Sheikh,, S. Davis,, E. C. Boedeker,, and J. P. Nataro. 2004. Use of a continuous-flow anaerobic culture to characterize enteric virulence gene expression. Infect. Immun. 72: 3793 3802.
47. Saleh, A.,, C. Figarella,, W. Kammouni,, S. Marchand-Pinatel,, A. Lazdunski,, A. Tubul,, P. Brun,, and M. D. Merten. 1999. Pseudomonas aeruginosa quorum-sensing signal molecule N- (3-oxododecanoyl)-L-homoserine lactone inhibits expression of P2Y receptors in cystic fibrosis tracheal gland cells. Infect. Immun. 67: 5076 5082.
48. Schauder, S.,, and B. L. Bassler. 2001. The languages of bacteria. Genes Dev. 15: 1468 1480.
49. Schauder, S.,, K. Shokat,, M. G. Surette,, and B. L. Bassler. 2001. The LuxS family of bacterial autoinducers: biosynthesis of a novel quorum-sensing signal molecule. Mol. Microbiol. 41: 463 476.
50. Shao, C. P.,, and L. I. Hor. 2001. Regulation of metalloprotease gene expression in Vibrio vulnificus by a Vibrio harveyi LuxR homologue. J. Bacteriol. 183: 1369 1375.
51. Sifri, C. D.,, E. Mylonakis,, K. V. Singh,, X. Qin,, D. A. Garsin,, B. E. Murray,, F. M. Ausubel,, and S. B. Calderwood. 2002. Virulence effect of Enterococcus faecalis protease genes and the quorum-sensing locus fsr in Caenorhabditis elegans and mice. Infect. Immun. 70: 5647 5650.
52. Singh, K. V.,, X. Qin,, G. M. Weinstock,, and B. E. Murray. 1998. Generation and testing of mutants of Enterococcus faecalis in a mouse peritonitis model. J. Infect. Dis. 178: 1416 1420.
53. Singh, P. K.,, A. L. Schaefer,, M. R. Parsek,, T. O. Moninger,, M. J. Welsh,, and E. P. Greenberg. 2000. Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms. Nature 407: 762 764.
54. Smith, R. S.,, E. R. Fedyk,, T. A. Springer,, N. Mukaida,, B. H. Iglewski,, and R. P. Phipps. 2001. IL-8 production in human lung fibroblasts and epithelial cells activated by the Pseudomonas autoinducer N-3-oxododecanoyl homoserine lactone is transcriptionally regulated by NF-kappa B and activator protein-2. J. Immunol. 167: 366 374.
55. Smith, R. S.,, S. G. Harris,, R. Phipps,, and B. Iglewski. 2002. The Pseudomonas aeruginosa quorum-sensing molecule N-(3- oxododecanoyl)homoserine lactone contributes to virulence and induces inflammation in vivo. J. Bacteriol. 184: 1132 1139.
56. Smith, R. S.,, and B. H. Iglewski. 2003. Pseudomonas aeruginosa quorum sensing as a potential antimicrobial target. J. Clin. Investig. 112: 1460 1465.
57. Sperandio, V.,, C. C. Li,, and J. B. Kaper. 2002. Quorumsensing Escherichia coli regulator A: a regulator of the LysR family involved in the regulation of the locus of enterocyte effacement pathogenicity island in enterohemorrhagic E. coli. Infect. Immun. 70: 3085 3093.
58. Sperandio, V.,, J. L. Mellies,, W. Nguyen,, S. Shin,, and J. B. Kaper. 1999. Quorum sensing controls expression of the type III secretion gene transcription and protein secretion in enterohemorrhagic and enteropathogenic Escherichia coli. Proc. Natl. Acad. Sci. USA 96: 15196 15201.
59. Sperandio, V.,, A. G. Torres,, J. A. Giron,, and J. B. Kaper. 2001. Quorum sensing is a global regulatory mechanism in enterohemorrhagic Escherichia coli O157:H7. J. Bacteriol. 183: 5187 5197.
60. Sperandio, V.,, A. G. Torres,, B. Jarvis,, J. P. Nataro,, and J. B. Kaper. 2003. Bacteria-host communication: the language of hormones. Proc. Natl. Acad. Sci. USA 100: 8951 8956.
61. Sperandio, V.,, A. G. Torres,, and J. B. Kaper. 2002. Quorum sensing Escherichia coli regulators B and C (QseBC): a novel two-component regulatory system involved in the regulation of flagella and motility by quorum sensing in E. coli. Mol. Microbiol. 43: 809 821.
62. Taga, M. E.,, and B. L. Bassler. 2003. Chemical communication among bacteria. Proc. Natl. Acad. Sci. USA 100 (Suppl. 2): 14549 14554.
63. Taga, M. E.,, S. T. Miller,, and B. L. Bassler. 2003. Lsr-mediated transport and processing of AI-2 in Salmonella typhimurium. Mol. Microbiol. 50: 1411 1427.
64. Telford, G.,, D. Wheeler,, P. Williams,, P. T. Tomkins,, P. Appleby,, H. Sewell,, G. S. Stewart,, B. W. Bycroft,, and D. I. Pritchard. 1998. The Pseudomonas aeruginosa quorum-sensing signal molecule N-(3-oxododecanoyl)-L-homoserine lactone has immunomodulatory activity. Infect. Immun. 66: 36 42.
65. Throup, J. P.,, M. Camara,, G. S. Briggs,, M. K. Winson,, S. R. Chhabra,, B. W. Bycroft,, P. Williams,, and G. S. Stewart. 1995. Characterisation of the yenI/yenR locus from Yersinia enterocolitica mediating the synthesis of two N-acylhomoserine lactone signal molecules. Mol. Microbiol. 17: 345 356.
66. Venter, J. C.,, K. Remington,, J. F. Heidelberg,, A. L. Halpern,, D. Rusch,, J. A. Eisen,, D. Wu,, I. Paulsen,, K. E. Nelson,, W. Nelson,, D. E. Fouts,, S. Levy,, A. H. Knap,, M. W. Lomas,, K. Nealson,, O. White,, J. Peterson,, J. Hoffman,, R. Parsons,, H. Baden- Tillson,, C. Pfannkoch,, Y. H. Rogers,, and H. O. Smith. 2004. Environmental genome shotgun sequencing of the Sargasso Sea. Science 304: 66 74.
67. Visick, K. L.,, J. Foster,, J. Doino,, M. McFall-Ngai,, and E. G. Ruby. 2000. Vibrio fischeri lux genes play an important role in colonization and development of the host light organ. J. Bacteriol. 182: 4578 4586
68. Wang, X. D.,, P. A. de Boer,, and L. I. Rothfield. 1991. A factor that positively regulates cell division by activating transcription of the major cluster of essential cell division genes of Escherichia coli. EMBO J. 10: 3363 3372.
69. Williams, P. 2002. Quorum sensing: an emerging target for antibacterial chemotherapy? Expert Opin. Ther. Targets 6: 257 274.
70. Winzer, K.,, K. R. Hardie,, and P. Williams. 2002. Bacterial cellto- cell communication: sorry, can’t talk now—gone to lunch! Curr. Opin. Microbiol. 5: 216 222.
71. Xavier, K. B.,, and B. L. Bassler. 2003. LuxS quorum sensing: more than just a numbers game. Curr. Opin. Microbiol. 6: 191 197.
72. Xu, J.,, M. K. Bjursell,, J. Himrod,, S. Deng,, L. K. Carmichael,, H. C. Chiang,, L. V. Hooper,, and J. I. Gordon. 2003. A genomic view of the human- Bacteroides thetaiotaomicron symbiosis. Science 299: 2074 2076.
73. Yarwood, J. M.,, and P. M. Schlievert. 2003. Quorum sensing in Staphylococcus infections. J. Clin. Investig. 112: 1620 1625.
74. Zhu, J.,, and J. J. Mekalanos. 2003. Quorum sensingdependent biofilms enhance colonization in Vibrio cholerae. Dev. Cell 5: 647 656.
75. Zhu, J.,, M. B. Miller,, R. E. Vance,, M. Dziejman,, B. L. Bassler,, and J. J. Mekalanos. 2002. Quorum-sensing regulators control virulence gene expression in Vibrio cholerae. Proc. Natl. Acad. Sci. USA 99: 3129 3134.

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