Chapter 16 : Role of Flagella in Mucosal Colonization

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in

Role of Flagella in Mucosal Colonization, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555817619/9781555813239_Chap16-1.gif /docserver/preview/fulltext/10.1128/9781555817619/9781555813239_Chap16-2.gif


In recent years, different studies of bacterial flagella have unmasked novel features regarding their complex and sophisticated structure as well as their biological relevance beyond motility. This chapter focuses on these new structural and functional features of flagella, with emphasis on their ability to favor adherence, colonization, penetration, and translocation by bacterial pathogens and the resulting activation of innate immunity. For most bacterial pathogens, flagella and flagellum-driven motility are recognized as essential elements in their virulence scheme. Klose and Mekalanos constructed an rpoN (encoding s)-null mutant of and found that this strain was defective in motility, flagellation, and colonization in the infant-mouse colonization assay. In this study, they also identified three flagellar regulatory genes (flrABC), among which flrA and flrC encode σ-activators; mutations in these two genes yielded mutants defective in colonization. Flagella purified from enterohemorrhagic (EHEC) and K-12 showed similar levels of interleukin-8 (IL-8) induction as those for H6 flagella, suggesting that this is a property of flagella of some pathogenic bacteria as well as some members of the normal flora. It is possible that the conserved regions play an important role in generating an optimal conformation of the hypervariable domain within the flagellin molecule and, in turn, on the flagellum filament in order to display proinflammatory epitopes effectively. Flagellar genes are highly conserved among gram-negative bacteria, and much similarity in structure and function exists.

Citation: Girón J. 2005. Role of Flagella in Mucosal Colonization, p 213-236. In Nataro J, Cohen P, Mobley H, Weiser J (ed), Colonization of Mucosal Surfaces. ASM Press, Washington, DC. doi: 10.1128/9781555817619.ch16

Key Concept Ranking

Type III Flagellar Export Apparatus
Major Histocompatibility Complex Class II
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1
Figure 1

Schematic representation of the flagellar structure and the TTSS. The basal body is composed of a series of rings (L, P, S, M, and C), which span the inner and outer membranes and represent the motor that propels the flagellum filament. The filament is connected to the basal body through a hook structure. The flagellin subunits are exported across the cell envelope through the basal body to be assembled in a helical pattern at the tip of the growing filament. The tubular structure is formed by 11 strands of protofilaments of longitudinal helical arrays of flagellin subunits. The cap protein serves as a modulator of flagellum synthesis and secretion of proteins. The virulence-associated TTSS is structurally similar to the flagellar apparatus. Shown here is the TTSS of EPEC, which is composed of several Esc proteins and directs the secretion and translocation of secreted proteins (Esp and Tir) to the host cell cytoplasm. Like flagella, the presence of coiled-coil domains present in EspA suggests the possibility of formation of protofilaments yielding an EspA tubular helical structure. OM, outer membrane; IM, inner membrane; CW, cell wall; CM, cell membrane.

Citation: Girón J. 2005. Role of Flagella in Mucosal Colonization, p 213-236. In Nataro J, Cohen P, Mobley H, Weiser J (ed), Colonization of Mucosal Surfaces. ASM Press, Washington, DC. doi: 10.1128/9781555817619.ch16
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2
Figure 2

Schematic representation of the role of flagella of EPEC in adherence and IL-8 induction. Intimin, bundle-forming pilus (BFP), and EspA fiber are well-recognized EPEC adhesins. The EspA fibers connected to the TTSS secrete proteins (Esp and Tir) involved in attaching and effacing (A/E) lesion formation. The extracellular bacteria are tethered through the bundle-forming pilus and possibly via rod-like pili. The wavy flagellar filaments interconnect the bacteria and may mediate direct binding to a receptor on the cell membrane and hypothetically pierce the cell membrane and inject flagellins or other proteins to the cytosol. It is documented that the flagella may activate IL-8 and induce inflammation, but it is uncertain whether this activation employs the TLR5 signaling pathway.

Citation: Girón J. 2005. Role of Flagella in Mucosal Colonization, p 213-236. In Nataro J, Cohen P, Mobley H, Weiser J (ed), Colonization of Mucosal Surfaces. ASM Press, Washington, DC. doi: 10.1128/9781555817619.ch16
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3
Figure 3

Role of flagella in biofilm formation. Shown is the model for biofilm formation by . The initial attachment of the bacteria to the abiotic surface is promoted by functional flagella and motility. Once attached, the bacteria employ type IV pilus-mediated twitching motility to spread out on the surface, with subsequent formation of aggregates that form three-dimensional domes or columns surrounded by exopolysaccharide material, which renders the bacteria resistant to many antimicrobials. The bacteria may dissociate from the columns to initiate a new community.

Citation: Girón J. 2005. Role of Flagella in Mucosal Colonization, p 213-236. In Nataro J, Cohen P, Mobley H, Weiser J (ed), Colonization of Mucosal Surfaces. ASM Press, Washington, DC. doi: 10.1128/9781555817619.ch16
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 4
Figure 4

Schematic representation of the mechanism of flagella-mediated inflammation by S. enterica. The salmonellae utilize flagellum-driven motility to cross the intestinal mucus barrier. These bacteria secrete abundant flagellin to the extracellular milieu; flagellin then translocates to the basolateral surface of epithelial cells, where it interacts specifically with TLR5, leading to MAPK/NF-κB activation pathways, resulting in the induction of proinflammatory molecules (IL-8 and CCL20), synthesis of nitric oxide synthase and human β-defensin 2. (hBD-2). FliC may also induce TNF-α release from PMN, monocytes (MN), promonocytes (ProMN), and dendritic cells (DC) via activation of TLR5. CCL20 is a potent activator of DC, while IL-8 is a potent recruiter of neutrophils (Ns). The end result is inflammation.

Citation: Girón J. 2005. Role of Flagella in Mucosal Colonization, p 213-236. In Nataro J, Cohen P, Mobley H, Weiser J (ed), Colonization of Mucosal Surfaces. ASM Press, Washington, DC. doi: 10.1128/9781555817619.ch16
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Aizawa, S. 2001. Bacterial flagella and type III secretion systems. FEMS Microbiol. Lett. 202:157164.
2. Andrade, A.,, J. A. Girón,, J. M. K. Amhaz,, L. R. Trabulsi,, and M. B. Martinez. 2002. Expression and characterization of flagella in non-motile enteroinvasive Escherichia coli isolated from diarrhea cases. Infect. Immun. 70:58825886.
3. Arora, S. K.,, B. W. Ritchings,, E. C. Almira,, S. Lory, and R. Ramphal. 1998. The Pseudomonas aeruginosa flagellar cap protein, FliD, is responsible for mucin adhesion. Infect. Immun. 66:10001007.
4. Allen-Vercoe, E.,, and M. J. Woodward. 1999. The role of flagella, but not fimbriae, in the adherence of Salmonella enterica serotype Enteriditis to chick gut explant. J. Med. Microbiol. 48:771780.
5. Allen-Vercoe, E. A. R., Sayers,, M. J. Woodward. 1999. Virulence of Salmonella enterica serotype Enteritidis aflagellate and afimbriate mutants in a day-old chick model. Epidemiol. Infect. 122:395402.
6. Attridge, S. R.,, and D. Rowley. 1983. The role of flagellum in the adherence of Vibrio cholerae. J. Infect. Dis. 147:864872.
7. Auvray, F.,, J. Thomas,, G. M. Fraser,, and C. Hughes. 2001. Flagellin polymerization control by a cytosolic export chaperone. J. Mol. Biol. 308:221229.
8. Badger, J. L.,, and V. L. Miller. 1998. Expression of invasin and motility are coordinately regulated in Yersinia enterocolitica. J. Bacteriol. 180:793800.
9. Barnich, N.,, J. Boudeau,, L. Claret,, and A. Darfeuille- Michaud. 2003. Regulatory and functional co-operation of flagella and type 1 pili in adhesive and invasive abilities of AIEC strain LF82 isolated from a patient with Crohn’s disease. Mol. Microbiol. 48:781794.
10. Blocker, A.,, K. Komoriya,, and S. Aizawa. 2003. Type III secretion systems and bacterial flagella: insights into their function from structural similarities. Proc. Natl. Acad. Sci. USA 100:30273030.
11. Bomchil, N.,, P. Watnick,, and R. Kolter. 2003. Identification and characterization of a Vibrio cholerae gene, mbaA, involved in maintenance of biofilm architecture. J. Bacteriol. 185:13841390.
12. Bonifield, H. R.,, and K. T. Hughes. 2003. Flagellar phase variation in Salmonella enterica is mediated by a posttranscriptional control mechanism. J. Bacteriol. 185:35673574.
13. Bosshardt, S. C.,, R. F. Benson,, and B. S. Fields. 1997. Flagella are a positive predictor for virulence in Legionella. Microb. Pathog. 23:107112.
14. Carsiotis, M.,, D. L. Weionstein,, H. Karch,, I. A. Holder,, A.D. O’Brien. 1984. Flagella of Salmonella typhimurium are a virulence factor in infected C57BL/6J mice. Infect. Immun. 46:814818.
15. Chaubal, L. H.,, and P. S. Holt. 1999. Characterization of swimming motility and identification of flagellar proteins in Salmonella pullorum isolates. Am. J. Vet. Res. 60:13221327.
16. Chilcott, G. S.,, and K. Hughes. 2000. Coupling of flagellar gene expression to flagellar assembly in Salmonella enterica serovar Typhimurium and Escherichia coli. Microbiol. Mol. Biol. Rev. 64:694708.
17. Chua, K. L.,, Y. Y. Chan,, and Y. H. Gan. 2003. Flagella are virulence determinants of Burkholderia pseudomallei. Infect. Immun. 71:16221629.
18. Ciacci-Woolwine, F.,, L. S. Kucera,, S. H. Richardson,, N. P. Iyer,, and S. B. Mizel. 1997. Salmonellae activate tumor necrosis factor alpha production in a human promonocytic cell line via a released polypeptide. Infect. Immun. 65:46244633.
19. Ciacci-Woolwine, F.,, I. C. Blomfield,, S. H. Richardson,, and S. B. Mizel. 1998. Salmonella flagellin induces tumor necrosis factor alpha in a human promonocytic cell line. Infect. Immun. 66:1271134.
20. Ciacci-Woolwine, F.,, P. F. McDermott,, and S. B. Mizel. 1999. Induction of cytokine synthesis by flagella from gram-negative bacteria may be dependent on the activation or differentiation state of human monocytes. Infect. Immun. 67: 51765185.
21. Clyne, M.,, T. Ocroinin,, S. Suerbaum,, C. Josenhans,, and B. Drumms. 2000. Adherence of isogenic flagellum negative mutants of Helicobacter pylori and Helicobacter mustelae to human and ferret gastric epithelial cells. Infect. Immun. 68:43354339.
22. Cordes, F. S.,, K. Komoriya,, E. Larquet,, S. Yang,, E. D. Egelman,, A. Blocker,, and S. M. Lea. 2003. Helical structure of the needle of the type III secretion system of Shigella flexneri. J. Biol. Chem. 278:1710317107.
23. Correa, N. E.,, C. M. Lauriano,, R. McGee,, and K. E. Klose. 2000. Phosphorylation of the flagellar regulatory protein FliC is necessary for Vibrio cholerae motility and enhanced colonization. Mol. Microbiol. 35:743755.
24. Czerucka, D.,, S. Dahan,, B. Mograbi,, B. Rossi,, and P. Rampal. 2001. Implication of mitogen-activated protein kinases in T84 cell responses to enteropathogenic Escherichia coli infection. Infect. Immun. 69:12981305.
25. de Grado, M.,, C. M. Rosenberger,, A. Gauthier,, B. A. Vallance,, and B. B. Finlay. 2001. Enteropathogenic Escherichia coli infection induces expression of the early growth response factor by activating mitogen-activated protein kinase cascades in epithelial cells. Infect. Immun. 69:62176224.
26. Delahay, R. M.,, and G. Frankel. 2002. Coiled-coil proteins associated with type III secretion systems: a versatile domain revisited. Mol. Microbiol. 45:905916.
27. de Oliveira Garcia, D.,, M. Dall’Agnol,, M. Rosales,, A. C. Azzuz,, M. B. Martinez,, and J. A. Girón. 2002. Characterization of flagella produced by clinical isolates of Stenotrophomonas maltophilia. Emerg. Infect. Dis. 8:918923.
28. DeShazer, D.,, P. J. Brett,, R. Carlton, and D. E. Woods. 1997. Mutagenesis of Burkholderia pseudomallei with Tn5- OT182: isolation of motility mutants and molecular characterization of the flagellin structural gene. J. Bacteriol. 179:21162125.
29. Dibb-Fuller, M. P.,, E. Allen-Vercoe,, C. J. Thorns,, and M. J. Woodward. 1999. Fimbriae- and flagella-mediated association with and invasion of culture epithelial cells by Salmonella enteritidis. Microbiology 145:10231031.
30.DiMango, E, H. J. Zar, R. Bryan, and A. Prince. 1995. Diverse Pseudomonas aeruginosa gene products stimulate respiratory epithelial cells to produce interleukin-8. J. Clin. Investig. 96:22042210.
31. Donnelly, M. A.,, and T. S. Steiner. 2002. Two nonadjacent regions in enteroaggregative Escherichia coli flagellin are required for activation of toll-like receptor 5. J. Biol. Chem. 277:4045640461.
32. Eaton, K. A.,, S. Suerbam,, C. Josenhans,, and S. Krakowka. 1996. Colonization of gnotobiotic piglets by Helicobacter pylori deficient in two flagellin genes. Infect. Immun. 64:24452448.
33. Eaves-Pyles, T. D.,, H. R. Wong,, K. Odoms,, and R. B. Pyles. 2001. Salmonella flagellin dependent proinflammatory responses are localized to the conserved amino and carboxyl regions of the protein. J. Immunol. 167:70097016.
34. Eubanks, E. R.,, M. N. Guentzel,, and L. J. Berry. 1977. Evaluation of surface components of Vibrio cholerae as protective immunogens. Infect. Immun. 15:533538.
35. Feldman, M.,, R. Bryan,, S. Rajan,, L. Scheffler,, S. Brunner,, H. Tang,, and A. Prince. 1998. Role of flagella in pathogenesis of Pseudomonas aeruginosa pulmonary infection. Infect. Immun. 66:4351.
36.Freter R., P. C. O’Brien, and M. S. Macsai. 1981. Role of chemotaxis in the association of motile bacteria with intestinal mucosa: in vivo studies. Infect. Immun. 34:234240.
37. Freter, R.,, B. Allweiss,, P. C. O’Brien,, S. A. Halstead,, and M. S. Macsai. 1981. Role of chemotaxis in the association of motile bacteria with intestinal mucosa: in vitro studies. Infect. Immun. 34:241249.
38. Freter, R.,, and P. C. O’Brien. 1981. Role of chemotaxis in the association of motile bacteria with intestinal mucosa: chemotactic responses of Vibrio cholerae and description of motile non-chemotactic mutants. Infect. Immun. 34:215221.
39. Galán, J. E.,, and A. Collmer. 1999. Type III secretion machines: bacterial devices for protein delivery into host cells. Science 284:13221328.
40. Gardel, C. L.,, and J. J. Mekalanos. 1996. Alterations in Vibrio cholerae motility phenotypes correlate with changes in virulence factor expression. Infect. Immun. 64:22462255.
41. Gavin, R.,, S. Merino,, M. Altarriba,, R. Canals,, J. G. Shaw,, and J. M. Tomas. 2003. Lateral flagella are required for increased cell adherence, invasion and biofilm formation by Aeromonas spp. FEMS Microbiol. Lett. 224:7783.
42. Gavin, R.,, A. A. Rabaan,, S. Merino,, J. M. Tomas,, I. Gryllos,, and J. G. Shaw. 2002. Lateral flagella of Aeromonas species are essential for epithelial cell adherence and biofilm formation. Mol. Microbiol. 43:383397.
43. Gewirtz, A. T.,, A. M. Siber,, J. L. Madara,, and B. A. Mc- Cormick. 1999. Orchestration of neutrophil movement by intestinal epithelial cells in response to Salmonella typhimurium can be uncoupled from bacterial internalization. Infect. Immun. 67:608617.
44. Gewirtz, A. T.,, P. O. Simon, Jr.,, C. K. Schmitt,, L. J. Taylor,, C. H. Hagedorn,, A. D. O’Brien,, A. S. Neish,, and J. L. Madara. 2001. Salmonella typhimurium translocates flagellin across intestinal epithelia, inducing a proinflammatory response. J. Clin. Investig. 107:99109.
45. Gewirtz, A. T.,, T. A. Navas,, S. Lyons,, P. J. Godowski,, and J. L. Madara. 2001. Cutting edge. Bacterial flagellin activates basolaterally expressed TLR5 to induce epithelial proinflammatory gene expression. J. Immunol. 167:18821885.
46. Ghigo, J. M. 2003. Are there biofilm-specific physiological pathways beyond a reasonable doubt? Res. Microbiol. 154: 18.
47. Girón, J. A. 1995. Expression of flagella and motility by Shigella. Mol. Microbiol. 18:6375.
48. Girón, J. A.,, A. G. Torres,, E. Freer,, and J. B. Kaper. 2002. The flagella of enteropathogenic Escherichia coli mediate adherence to epithelial cells. Mol. Microbiol. 44:361379.
49. Golden, N. J.,, and D. W. K. Acheson. 2002. Identification of motility and autoagglutination Campylobacter jejuni mutants by random transposon mutagenesis. Infect. Immun. 70:17611771.
50. Grant, C. C. R.,, M. E. Konkel,, W. Cieplak, Jr.,, and L. S. Tompkins. 1993. Role of flagella in adherence, internalization and translocation of Campylobacter jejuni in nonpolarized and polarized epithelial cell cultures. Infect. Immun. 61:17641771.
51. Gupta, S.,, and R. Chowdhruy. 1997. Bile affects production of virulence factors and motility of Vibrio cholerae. Infect. Immun. 65:11311134
52. Hase, C. C. 2001. Analysis of the role of flagella activity in virulence gene expression in Vibrio cholerae. Microbiology 147:831837.
53. Harshey, R. M. 2003. Bacterial motility on a surface. Annu. Rev. Microbiol. 57:249273.
54. Hawn, T. R.,, A. Verbon,, K. D. Lettinga,, L. P. Zhao,, S. S. Li,, R. J. Laws,, S. J. Skerrett,, B. Beutler,, L. Schroeder,, A. Nachman,, A. Ozinsky,, K. D. Smith,, and A. Aderem. 2003. A common dominant TLR5 stop codon polymorphism abolishes flagellin signaling and is associated with susceptibility to Legionnaires’ disease. J. Exp. Med. 198:15631572.
55. Hayashi, F.,, K. D. Smith,, A. Ozinsky,, T. R. Hawn,, E. C. Yi,, D. R. Goodlett,, J. K. Eng,, S. Akira,, D. M. Underhill,, and A. Aderem. 2001]. The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 410:10991103.
56. Hueck, C. J. 1998. Type III protein secretion systems in bacterial pathogens of animals and plants. Microbiol. Mol. Biol. Rev. 62:379433.
57. Hybiske,, K. J. K. Ichikawa,, V. Huang,, S. J. Lory, and T. E. Machen. 2004. Cystic fibrosis airway epithelial cell polarity and bacterial flagellin determine host response to Pseudomonas aeruginosa. Cell. Microbiol. 6:4963.
58. Ikeda, J. S.,, C. K. Schmitt,, S. C. Darnell,, P. R. Watson,, J. Bispham,, T. S. Wallis,, D. L. Weinstein,, E. S. Metcalf,, P. Adams,, C. D. O’Connor,, and A. D. O’Brien. 2001. Flagellar phase variation of Salmonella enterica serovar Typhimurium contributes to virulence in the murine typhoid infection model but does not influence Salmonella-induced enteropathogenesis. Infect. Immun. 69:30123030.
59. Iriarte, M. I., Stainier,, A. V. Mikulskis,, and G. R. Conelis. 1995. The fliA gene encoding σ-28 in Yersinia enterocolitica. J. Bacteriol. 177:22992304.
60. Jacchieri, S. G.,, R. Torquato,, and R. R. Brentani. 2003. Structural study of binding of flagellin by toll-like receptor 5. J. Bacteriol. 185:42434247.
61. Jones, G. W.,, L. A. Richardson,, and D. Uhlman. 1981. The invasion of HeLa cells by Salmonella typhimurium: reversible and irreversible bacterial attachment and the role of bacterial motility. J. Gen. Microbiol. 127:351360.
62. Jones, B. D.,, C. A. Lee,, and S. Falkow. 1992. Invasion by Salmonella typhimurium is affected by the direction of flagellar rotation. Infect. Immun. 60:24732480.
63. Josenhans, C.,, and S. Suerbaum. 2002. The role of motility as a virulence factor in bacteria. Int. J. Med. Microbiol. 291:605614.
64. Kaisho, T.,, and S. Akira. 2002. Toll-like receptors as adjuvant receptors. Biochim. Biophys. Acta 1589:113.
65. Khoramian-Falsafi, T.,, S. Harayama,, K. Kutsukake,, and J. C. Pechere. 1990. Effect of motility and chemotaxis on the invasion of Salmonella typhimurium into HeLa cells. Microb. Pathog. 9:4753.
66. Kim, J. S.,, J. H. Chang,, S. I. Chung,, and J. S. Yum. 1999. Molecular cloning and characterization of the Helicobacter pylori fliD gene, an essential factor in flagellar structure and motility. J. Bacteriol. 181:69696976.
67. Kimbrough, T. G.,, and S. I. Miller. 2002. Assembly of the type III secretion needle complex of Salmonella typhimurium. Microb. Infect. 4:7582.
68. Kirov, S. M. 2003. Bacteria that express lateral flagella enable dissection of the multifunctional roles of flagella in pathogenesis. FEMS Microbiol. Lett. 224:151159.
69. Klausen M.,, A. Aaes-Jorgensen,, S. Molin,, and T. Nielsen. 2003. Involvement of bacterial migration in the development of complex multicellular structures in Pseudomonas aeruginosa biofilms. Mol. Microbiol. 50:6168.
70. Klausen M.,, A. Heydorn,, P. Ragas,, L. Lambertsen,, A. Aaes- Jorgensen,, S. Molin,, and T. Nielsen. 2003. Biofilm formation by Pseudomonas aeruginosa wild type, flagella and type IV pili mutants. Mol. Microbiol. 48:15111524.
71. Klemm, P.,, and M. A. Schembri. 2000. Bacterial adhesins: function and structure. Int. J. Med. Microbiol. 290:2735.
72. Klose, K. E.,, and J. J. Mekalanos. 1998. Distinct roles of an alternative sigma factor during both free-swimming and colonizing phases of the Vibrio cholerae pathogenic cycle. Mol. Microbiol. 28:501520.
73. Knutton, S.,, I. Rosenshine,, M. J. Pallen,, I. Nisan,, B. C. Neves,, C. Bain,, C. Wolff,, G. Dougan,, and G. Frankel. 1998. A novel EspA-associated surface organelle of enteropathogenic Escherichia coli involved in protein translocation into epithelial cells. EMBO J. 17:21662176.
74. Komoriya, K.,, N. Shibano,, T. Higano,, N. Azuma,, S. Yamaguchi,, and S. Aizawa. 1999. Flagellar proteins and type IIIexported virulence factors are the predominant proteins secreted into the culture media of Salmonella typhimurium. Mol. Microbiol. 34:767779.
75. Kubori, T.,, Y. Matsushima,, D. Nakamura,, J. Uralil,, M. Lara- Tejero,, A. Sukhan,, J.E. Galán,, and S. I. Aizawa. 1998. Supramolecular structure of the Salmonella typhimurium type III protein secretion system. Science 280:602605.
76. Krukonis, E. S.,, and V. J. DiRita. 2003. From motility to virulence: sensing and responding to environmental signals in Vibrio cholerae. Curr. Opin. Microbiol. 6:186190.
77. Lahteenmaki, K.,, B. Westerlund,, P. Kuusela,, and T. K. Korhonen. 1993. Immobilization of plasminogen on Escherichia coli flagella. FEMS Microbiol. Lett. 106:309314.
78. La Ragione, R. M.,, A. R. Sayers,, and M. J. Woodward. 2000. The role of fimbriae and flagella in the colonization, invasion and persistence of Escherichia coli O78:K80 in the day-oldchick model. Epidemiol. Infect. 124:351363.
79. La Ragione, R. M.,, W. A. Cooley,, P. Velge,, M. A. Jepson,, and M. J. Woodward. 2003. Membrane ruffling and invasion of human avian cell lines is reduced for flagellate mutants of Salmonella enterica serotype Enteritiditis. Int. J. Med. Microbiol. 293:261272.
80. Lee, M. D.,, R. Curtiss III,, and T. Peay. 1996. The effect of bacterial surface structures on the pathogenesis of S. typhimurium infection in chickens. Avian Dis. 40:2836.
81. Lee, S. K.,, A. Stack,, E. Katzowitsch,, S. I. Aizawa,, S. Suerbaum,, and C. Josenhans. 2003. Helicobacter pylori flagellins have very low intrinsic activity to stimulate human gastric epithelial cells via TLR5. Microb. Infect. 5:13451356.
82. Li, X.,, D. A. Rasko,, C. V. Lockatell,, D. E. Johnson,, and H. L. T. Mobley. 2001. Repression of bacterial motility by a novel fimbrial gene product. EMBO J. 20:48544862.
83. Liaudet, L. , K,, G. K. Murthy,, J. G. Mabley,, P. Pacher,, F. G. Soriano,, A. L. Salzman,, and C. Szabo. 2002. Comparison of inflammation, organ damage and oxidant stress induced by Salmonella enterica serovar Muenchen flagellin and serovar Enteritidis lipopolysaccharide. Infect. Immun. 70: 192198.
84. Liaudet, L.,, C. Szabo,, O. V. Evgenov,, K. G. Murthy,, P. Pacher,, L. Virag,, J. G. Mabley,, A. Marton,, F. G. Soriano,, M. Y. Kirov,, L. J. Bjertnaes,, and A. L. Salzman. 2003. Flagellin from gram-negative bacteria is a potent mediator of acute pulmonary inflammation in sepsis. Shock19:131137.
85. Lillard H. S. 1986. Role of fimbriae and flagella in the attachment of Salmonella typhimurium to poultry skin. J. Food Sci. 51:5457.
86. Lillehoj, E. P.,, B. T. Kim,, and K. C. Kim. 2002. Identification of Pseudomonas aeruginosa flagellin as an adhesin for Muc1 mucin. Am. J. Physiol. Ser. L 282:L751L756.
87. Liu, S.-L.,, T. Ezaaki,, H. Miura,, K. Matsui,, and E. Yabuuchi. 1988. Intact motility as a Salmonella typhi invasion related factor. Infect. Immun. 56:19671973.
88. Liu, X.,, and P. Matsumara. 1994. The FlhD/FlhC complex, a transcriptional activator of the Escherichia coli flagellar class II operons. J. Bacteriol. 176:73457351.
89. Lupas, A.,, M. Van Dyke,, and J. Stock. 1991. Predicting coiled coils from protein sequences. Science 252:11621164.
90. MacNab, R. M. 1999. The bacterial flagellum: reversible rotary propeller and type III export apparatus. J. Bacteriol. 181:71497153.
91. MacNab, R. M. 2000. Type III protein pathway exports Salmonella flagella. ASM News 66:738745.
92. MacNab, R. M. 2003. How bacteria assemble flagella. Annu. Rev. Microbiol. 57:77100.
93. McDermott, P. E.,, F. Ciacci-Woolwine,, J. A. Snipes,, and S. B. Mizel. 2000. High-affinity interaction between gram-negative flagellin and a cell surface polypeptide results in human monocyte activation. Infect. Immun. 10:55255529.
94. McGee, D. J.,, C. Coker,, T. L. Testerman,, J. M. Harro,, S. V. Gibson,, and H. L. T. Mobley. 2002. The Helicobacter pylori fibA, flagellar biosynthesis and regulatory gene is required for motility and virulence and modulates urease of H. pylori and Proteus mirabilis. J. Med. Microbiol. 51:958970.
95. McNamara, N.,, and C. Basbaum. 2002. Mechanism by which bacterial flagellin stimulates host mucin production. Adv. Exp. Med. Biol. 506:269273.
96. McSorley, S. J.,, B. D. Ehst,, Y. Yu,, and A. T. Gewirtz. 2002. Bacterial flagellin is an effective adjuvant for CD4+ T cells in vivo. J. Immunol. 169:39143919.
97. Means, T. K.,, F. Hayashi,, K. D. Smith,, A. Aderem,, and A. D. Luster. 2003. The toll-like receptor 5 stimulus: bacterial flagellin induces maturation and chemokine production in human dendritic cells. J. Immunol. 170:51655175.
98. Medzhitov, R. 2001. Toll-like receptors and innate immunity. Nat. Rev. Immunol. 1:135145.
99. Mimori-Kyouse, Y.,, F. Vonderviszt,, and K. Namba. Locations of terminal segments of flagellin in the filament structure and their roles in polymerization and polymorphism. J. Mol. Biol. 270:222237.
100. Mizel, S. B.,, and J. A. Snipes. 2002. Gram-negative flagellin-induced self-tolerance is associated with a block in interleukin- 1 receptor-associated kinase release from Toll-like receptor 5. J. Biol. Chem. 277:2241422420.
101. Mizel, S. B.,, A. P. West,, and R. R. Hantgan. 2003. Identification of a sequence in human toll-like receptor 5 required for the binding of gram-negative flagellin. J. Biol. Chem. 278:2362423629.
102. Mobley, H. T.,, B. Belas,, V. Lockatell,, G. Chippendale,, A. L. Trifillis,, D. E. Johnson,, and J. W. Warren. 1996. Construction of a flagellum-negative mutant of Proteus mirabilis: effect on internalization by human renal epithelial cells and virulence in a mouse model of ascending urinary tract infections. Infect. Immun. 64:53325340.
103. Montie, T. C.,, D. Doyle-Huntzinger,, R. C. Craven,, and I. A. Holder. 1982. Loss of virulence associated with absence of flagellum in an isogenic mutant of Pseudomonas aeruginosa in the burned-mouse model. Infect. Immun. 38:12961298.
104. Moreira, C. G.,, S. M. Carneiro,, J. P. Nataro,, L. R. Travulsi,, and W. P. Elias. 2003. Role of type 1 fimbriae in the aggregative adhesion pattern of enteroaggregative Escherichia coli. FEMS Microbiol. Lett. 226:7985.
105. Morooka, T.,, A. Umeda,, and K. Amako. 1985. Motility as an intestinal colonization factor for Campylobacter jejuni. J. Gen. Microbiol. 131:19731980.
106. Murthy, K. B.,, A. Deb,, S. Goonesekere,, C. Szabo,, and A. L. Salzman. 2003. Identification of conserved domains in Salmonella muenchen flagellin that are essential for its ability to activate TLR5 and to induce an inflammatory response in vitro. J. Biol. Chem. 279:56675675.
107. Muzio, M.,, and A. Mantovani. 2000. Toll-like receptors. Microbes Infect. 2:251255.
108. Nachamkin, I,, X.-H. Yang, and N. J. Stern. 1993. Role of Campylobacter jejuni flagella as colonization factors for three-day old chicks: analysis with flagellar mutants. Appl. Environ. Microbiol. 59:12691273.
109. Nataro, J. P.,, and J. B. Kaper. 1998. Diarrheagenic Escherichia coli. Clin. Microbiol. Rev. 11:142201.
110. Nelson, E. T.,, J. D. Clements,, and R. A. Finkelstein. 1976. Vibrio cholerae adherence and colonization in experimental cholera: electron microscopic studies. Infect. Immun. 14: 527547.
111. Ogushi, K.,, A. Wada,, T. Niidome,, N. Mori,, K. Oishi,, T. Nagatake,, A. Takahashi,, A. Asakura,, S. Makino,, H. Hojo,, Y. Nakahara,, M. Ohsaki,, T. Hatakeyama,, H. Aoyagi,, H. Kurazono,, J. Moss,, and T. Hirayama. 2001. Salmonella enteritidis FliC (flagella filament protein) induces human β- defensin-2 mRNA production by Caco-2 cells. J. Biol. Chem. 276:3052130526.
112. Ormonde, P.,, P. Horstedt,, R. O’Toole,, and D. L. Milton. 2000. Role of motility in adherence to and invasion of a fish cell line by Vibrio anguillarum. J. Bacteriol. 182:23262328.
113. O’Toole, G. A.,, and R. Kolter. 1998. Flagellar and twitching motility are necessary for Pseudomonas aeruginosa biofilm development. Mol. Microbiol. 30:295304.
114. Ottemann, K. M.,, and A. C. Lowenthal. 2002. Helicobacter pylori uses motility for initial colonization and to attain robust infection. Infect. Immun. 70:19841990.
115. Pallen, M. J. 1997. Coiled-coil domains in proteins secreted by type III secretion systems. Mol. Microbiol. 25:423425.
116. Parker, C. T., and J. Guard-Petter. 2001. Contribution of flagella and invasion proteins to pathogenesis of Salmonella enterica serovar Enteritidis in chicks. FEMS Microbiol. Lett. 204:287291.
117. Pavlovskis, O. R.,, D. M. Rollins,, R. L. Haberberger, Jr.,, A. E. Green,, L. Habash,, S. Strocko,, and R. I. Walker. 1991. Significance of flagella in colonization resistance of rabbits immunized with Campylobacter spp. Infect. Immun. 59:22592264.
118. Peel,, M. W. Donachie,, and A. Shaw. 1988. Temperature-dependent expression of flagella of Listeria monocytogenes studied by electron microscopy, SDS-PAGE and western blotting. J. Gen. Microbiol. 134:21712178.
119. Plano, G. V.,, J. B. Day,, and F. Ferracci. 2001. Type III export: new uses for an old pathway. Mol. Microbiol. 40:284293.
120. Postnova, T.,, O. G. Gomez-Duarte,, and K. Richardson. 1996. Motility mutants of Vibrio cholerae O1 have reduced adherence in vitro to human small intestinal epithelial cells as demonstrated by ELISA. Microbiology 142:27672776.
121. Pratt, L. A.,, and R. Kolter. 1998. Genetic analysis of Escherichia coli biofilm formation: roles of flagella, motility, chemotaxis and type I pili. Mol. Microbiol. 30:285293.
122. Pruckler, J. M.,, R. F. Benson,, M. Moyenuddi,, W. T. Martin,, and B. S. Fields. 1995. Association of flagellum expression and intracellular growth of Legionella pneumophila. Infect. Immun. 63:49284932.
123. Rabaan, A. A.,, I. Gryllos,, J. M. Tomas,, and J. G. Shaw. 2001. Motility and the polar flagellum are required for Aeromonas caviae adherence to HEp-2 cells. Infect. Immun. 69:42574267..
124. Ramphal, R.,, S. K. Arora,, and B. W. Ritchings. 1996. Recognition of mucin by the adhesin-flagellar system of Pseudomonas aeruginosa. Am. J. Respir. Crit. Care Med. 154:S170S174.
125. Read, R. C.,, and D. H. Wyllie. 2001. Toll receptors and sepsis. Curr. Opin. Crit. Care 7:371375.
126. Reed, K. A.,, M. E. Hobert,, C. E. Kolenda,, K. A. Sands,, M. Rathman,, M. O’Connor,, S. Lyons,, S. A. T. Gewirtz,, P. J. Sansonetti,, and J. L. Madara. 2002. The Salmonella typhimurium flagellar basal body protein FliE is required for flagellin production and to induce a proinflammatory response in epithelial cells. J. Biol. Chem. 277:1334613353.
127. Reid, S. D.,, R. Selander,, and T. S. Whittam. 1999. Sequence diversity of flagellin (FliC) alleles in pathogenic Escherichia coli. J. Bacteriol. 181:153160.
128. Richardson, K. 1991. Roles of motility and flagellar structure in pathogenicity of Vibrio cholerae: analysis of motility mutants in three animal models. Infect. Immun. 59:27272736.
129. Robertson, J. M.,, G. Grant,, E. Allen-Vercoe,, M. J. Woodward,, A. Pusztai,, and H. J. Flint. 2000. Adhesion of Salmonella enterica var Enteritidis strains lacking fimbriae and flagella to rat ileal explants cultured at the air interface or submerged in tissue culture medium. J. Med. Microbiol. 49:691969.
130. Robertson, J. M.,, N. H. McKenzie,, M. Duncan,, E. Allen- Vercoe,, M. J. Woodward,, and H. J. Flint. 2003. Lack of flagella disadvantages Salmonella enterica serovar Enteritidis during the early stages of infection in the rat. J. Med. Microbiol. 52:9199.
131. Sadziene, A.,, D. D. Thomas,, V. G. Bundoc,, S. C. Holt,, and A. G. Barbour. 1991. A flagella-less mutant of Borrelia burgdorferi. Structural, molecular and in vitro functional characterization. J. Clin. Investig. 88:8292.
132. Samatey, F. A.,, K. Imada,, S. Nagashima,, F. Venderviszt,, T. Kumasaka,, M. Yamamoto,, and K. Namba. 2001. Structure of the bacterial flagellar protofilament and implications for a switch for supercoiling. Nature 410:331337.
133. Schilling, J. D.,, S. M. Matin,, C. S. Hung,, R. G. Lorenz,, S. J. Hultgren. 2003. Toll-like receptor 4 on stomal and hematopoietic cells mediate innate resistance to uropathogenic Escherichia coli. Proc. Natl. Acad. Sci. USA 100:42034208.
134. Schmiel, D. H.,, G. M. Young,, and V. L. Miller. 2000. The Yersinia enterocolitica phospholipase gene yplA is part of the flagellar regulon. J. Bacteriol. 182:23142320.
135. Schmitt, C. K.,, J. S. Ikeda,, S. C. Darnell,, P. R. Watson,, J. Bispham,, T. S. Wallis,, D. L. Weinstein,, E. S. Metcalf,, and A. D. O’Brien. 2001. Absence of all components of the flagellar export and synthesis machinery differentially alters virulence of Salmonella enterica serovar Typhimurium in models of typhoid fever, survival in macrophages, tissue culture invasiveness and calf enterocolitis. Infect. Immun. 69:56195625.
136. Sellek, R. E.,, R. Escudero,, H. Gil,, I. Rodriguez,, E. Chaparro,, E. Perez-Pastrana,, A. Vivo,, and P. Anda. 2002. In vitro culture of Borrelia garinii results in loss of flagella and decreased invasiveness. Infect. Immun. 70:48514858.
137. Sheikh J,, S. Hicks,, M. Dall’Agnol,, A. D. Phillips,, and J. P. Nataro. 2001 Roles for Fis and YafK in biofilm formation by enteroaggregative Escherichia coli. Mol. Microbiol. 5:983997.
138. Sierro, F.,, B. Dubois,, A. Coste,, D. Kaiserlian, Kraehenbuhl, and J. Sirard. 2001. Flagellin stimulation of intestinal epithelial cells triggers CCL20 mediated migration of dendritic cells. Proc. Natl. Acad. Sci. USA 98:1372213727.
139. Smith, K. D.,, and A. Ozinsky. 2002. Toll-like receptor-5 and the innate immune response to bacterial flagellin. Curr. Top. Microbiol. Immunol. 270:93108.
140. Smith, M. F.,, A. Mitchell,, G. Li,, S. Ding,, A. M. Fitzmaurice,, K. Ryan,, S. Crowe,, and J. R. Goldberg. 2003. Toll-like receptor (TLR) 2 and TLR5 but not TLR4, are required for Helicobacter pylori-induced NF-κB activation and chemokine expression by epithelial cells. J. Biol. Chem. 278:3255232560.
141. Smith, K. D.,, E. Andersen-Nissen,, F. Hayashi,, K. Strobe,, M. A. Bergman,, S. L. Rassoulian Barrret,, B. T. Cookson, and A. Aderem. 2003. Toll-like receptor 5 recognizes a conserved site on flagellin required for protofilament formation and bacterial motility. Nat. Immunol. 4:12471253.
142. Sperandio, V.,, A. G. Torres,, J. A. Girón,, and J. B. Kaper. 2001. Quorum sensing is a global regulatory mechanism in enterohemorrhagic Escherichia coli O157:H7. J. Bacteriol. 183:51875197.
143. Steiner, T. S.,, A. A. Lima,, J. P. Nataro,, and R. L. Guerrant. 1998. Enteroaggregative Escherichia coli produce intestinal inflammation and growth impairment and cause interleukin- 8 release from intestinal epithelial cells. J. Infect. Dis. 177:8896.
144. Steiner, T. S.,, J. P. Nataro,, C. E. Poteet-Smith,, J. A. Smith,, and R. L. Guerrant. 2000. Enteroaggregative Escherichia coli expresses a novel flagellin that causes IL-8 release from intestinal epithelial cells. J. Clin. Investig. 105:17691777.
145. Szymanski, C. M.,, M. King,, M. Haardt,, and G. D. Armstrong. 1995. Campylobacter jejuni motility and invasion of Caco-2 cells. Infect. Immun. 3:42954300.
146. Takahashi, A.,, A. Wada,, K. Ogushi,, K. Maeda,, T. Kawahara,, K. Mawatari,, H. Kurazono,, J. Moss,, T. Hirayama,, and Y. Nakaya. 2001. Production of β-defensin-2 by human colonic epithelial cells induced by Salmonella enteritidis flagella filament structural protein. FEBS Lett. 508:484488.
147. Tasteyre, A.,, M. Barc,, A. Collignon,, H. Boureau,, and T. Karjalainen. 2001. Role of FliC and FliD flagellar proteins of Clostridium difficile in adherence and gut colonization. Infect. Immun. 69:79377940.
148. Teppema, J. S.,, P. A. M. Guinée,, A. A. Abrahim,, M. Páques,, and E. J. Ruitenberg. 1987. In vivo adherence and colonization of Vibrio cholerae strains that differ in hemagglutinating activity and motility. Infect. Immun. 55:20932102.
149. Tomich, M.,, C. A. Herfst,, J. W. Golden,, and C. D. Mohr. 2002. Role of flagella in host cell invasion by Burkholderia cepacia. Infect. Immun. 70:17991806.
150. Underhill, D. M.,, and A. Ozinsky. 2002. Toll-like receptors: key mediators of microbe detection. Curr. Opin. Immunol. 14:103110.
151. Van Asten F. J. A. M.,, H. G. C. J. M. Hendriks,, J. F. J. G. Koninkx,, B. A. M. Van der Zeijst,, and W. Gaastra. 2000. Inactivation of the flagellin gene of Salmonella enterica serotype Enteritidis strongly reduces invasion into differentiated caco-2 cells. FEMS Microbiol. Lett. 185:175179.
152. Walker, S. L.,, M. Sojka,, M. Dibb-Fuller,, and M. J. Woodward. 1999. Effect of pH, temperature and surface contact on the elaboration of fimbriae and flagella by Salmonella serotype Enteritidis. J. Med. Microbiol. 48:253261.
153. Watnick, P. I.,, C. M. Lauriano,, K. E. Klose,, L. Croal,, and R. Kolter. 2001. The absence of a flagellum leads to altered colony morphology, biofilm development and virulence in Vibrio cholerae O139. Mol. Microbiol. 39:223235.
154. Watnick, P. I.,, and R. Kolter. 1999. Steps in the development of a Vibrio cholerae El Tor biofilm. Mol. Microbiol. 34:586595.
155. Way, S. S.,, L. J. Thompson,, J. E. Lopes,, A. M. Hajjar,, T. R. Kollmann,, N. E. Freitag,, and C. B. Wilson. 2004. Characterization of flagellin expression and its role in Listeria monocytogenes infection and immunity. Cell. Microbiol. 6:235242.
156. Weinstein, D. L.,, M. Carsiotis,, C. R. Lissner,, and A. D. O’Brien. 1984. Flagella help Salmonella typhimurium survive within murine macrophages. Infect. Immun. 46:819825.
157. Wyant, T. L.,, M. K. Tanner,, and M. B. Sztein. 1999. Salmonella typhi flagella are potent inducers of proinflammatory cytokine secretion by human monocytes. Infect. Immun. 67: 36193624.
158. Wyant, T. L.,, M. K. Tanner,, and M. B. Sztein. 1999. Potent immunoregulatory effects of Salmonella typhi flagella on antigenic stimulation of human peripheral blood mononuclear cells. Infect. Immun. 67:13381346.
159. Yancey, R. J.,, D. L. Willis,, and L. J. Berry. 1978. Role of motility in experimental cholera in adult rabbits. Infect. Immun. 22:387392.
160. Yao, R.,, D. H. Burr,, P. Doig,, T. J. Trust,, H. Niu,, and P. Guerry. Isolation of motile and non-motile insertional mutants of Campylobacter jejuni: the role of motility in adherence and invasion of eukaryotic cells. Mol. Microbiol. 14:883893.
161. Yonekura, K.,, S. Maki,, D. G. Morgan,, D. J. DeRosier,, F. Vonderviszt,, K. Imada,, and K. Namba. 2000. The bacterial flagellar cap as the rotary promoter of flagellin self-assembly. Science 290:21482152.
162. Yonekura, K.,, S. Yonekura,, and K. Namba. 2002. Growth mechanism of the bacterial flagellar filament. Res. Microbiol. 153:191197.
163. Yonekura, K.,, S. Yonekura,, and K. Namba. 2003. Complete atomic model of the bacterial flagellar filament by electron cryomicroscopy. Nature 424:643650.
164. Young, G. M.,, M. J. Smith,, S. A. Minnich,, and V. L. Miller. 1999. The Yersinia enterocolitica motility master regulatory operon, fihDC, is required for flagellin production, swimming motility and swarming motility. J. Bacteriol. 181:28232833.
165. Young, G. M.,, D. H. Schmiel,, and V. L. Miller. 1999. A new pathway for the secretion of virulence factors by bacteria: the flagellar export apparatus functions as a protein secretion system. Proc. Natl. Acad. Sci. USA 96:64566461.
166. Young, G. M.,, J. L. Badger,, and V. L. Miller. 2000. Motility is required to initiate host cell invasion by Yersinia enterocolitica. Infect. Immun. 68:43234326.
167. Young, B. M.,, and G. M. Young. 2002. Yp1A is exported by the Ysc, Ysa and flagellar type III secretion systems of Yersinia enterocolitica. J. Bacteriol. 184:13241334.
168. Zeng, H.,, A. Q. Carlson,, Y. Guo,, Y. Yu,, L. S. Collier-Hyams,, J. L. Madara,, A. T. Gewirtz,, and A.S. Neish. 2003. Flagellin is the major proinflammatory determinant of enteropathogenic Salmonella. J. Immunol. 171:36683674.
169. Zhang, J,, K. Xu,, B. Ambati,, and F-S. X. Yu. 2003. Toll-like receptor-5 mediated corneal epithelial inflammatory responses to Pseudomonas aeruginosa flagellin. Investig. Ophthalmol. Visual Sci. 44:42474254.
170. Zhou, X.,, J. A. Girón,, A. G. Torres,, J. A. Crawford,, E. Negrete,, S. N. Vogel,, and J. B. Kaper. 2003. Flagellin of enteropathogenic Escherichia coli stimulates interleukin-8 production in T84 cells. Infect. Immun. 71:21202129.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error