No metrics data to plot.
The attempt to load metrics for this article has failed.
The attempt to plot a graph for these metrics has failed.

EcoSal Plus

Domain 8:


Pili Assembled by the Chaperone/Usher Pathway in and

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.
Buy article
Choose downloadable ePub or PDF files.
Buy this Chapter
Digital (?) $30.00
  • Authors: Glenn T. Werneburg1, and David G. Thanassi3
  • Editor: Michael S. Donnenberg5
    Affiliations: 1: Department of Molecular Genetics and Microbiology; 2: Center for Infectious Diseases, Stony Brook University, Stony Brook, NY 11794; 3: Department of Molecular Genetics and Microbiology; 4: Center for Infectious Diseases, Stony Brook University, Stony Brook, NY 11794; 5: Virginia Commonwealth University School of Medicine, Richmond, VA
  • Received 06 September 2017 Accepted 16 January 2018 Published 13 March 2018
  • Address correspondence to David G. Thanassi, david.thanassi@stonybrook.edu
image of Pili Assembled by the Chaperone/Usher Pathway in <span class="jp-italic">Escherichia coli</span> and <span class="jp-italic">Salmonella</span>
    Preview this reference work article:
    Zoom in

    Pili Assembled by the Chaperone/Usher Pathway in and , Page 1 of 2

    | /docserver/preview/fulltext/ecosalplus/8/1/ESP-0007-2017-1.gif /docserver/preview/fulltext/ecosalplus/8/1/ESP-0007-2017-2.gif
  • Abstract:

    Gram-negative bacteria assemble a variety of surface structures, including the hair-like organelles known as pili or fimbriae. Pili typically function in adhesion and mediate interactions with various surfaces, with other bacteria, and with other types of cells such as host cells. The chaperone/usher (CU) pathway assembles a widespread class of adhesive and virulence-associated pili. Pilus biogenesis by the CU pathway requires a dedicated periplasmic chaperone and integral outer membrane protein termed the usher, which forms a multifunctional assembly and secretion platform. This review addresses the molecular and biochemical aspects of the CU pathway in detail, focusing on the type 1 and P pili expressed by uropathogenic as model systems. We provide an overview of representative CU pili expressed by and , and conclude with a discussion of potential approaches to develop antivirulence therapeutics that interfere with pilus assembly or function.

  • Citation: Werneburg G, Thanassi D. 2018. Pili Assembled by the Chaperone/Usher Pathway in and , EcoSal Plus 2018; doi:10.1128/ecosalplus.ESP-0007-2017


1. Thanassi DG, Bliska JB, Christie PJ. 2012. Surface organelles assembled by secretion systems of Gram-negative bacteria: diversity in structure and function. FEMS Microbiol Rev 36:1046–1082.
2. Costa TR, Felisberto-Rodrigues C, Meir A, Prevost MS, Redzej A, Trokter M, Waksman G. 2015. Secretion systems in Gram-negative bacteria: structural and mechanistic insights. Nat Rev Microbiol 13:343–359.
3. Proft T, Baker EN. 2009. Pili in Gram-negative and Gram-positive bacteria - structure, assembly and their role in disease. Cell Mol Life Sci 66:613–635.
4. Ottow JC. 1975. Ecology, physiology, and genetics of fimbriae and pili. Annu Rev Microbiol 29:79–108.
5. Duguid JP, Smith IW, Dempster G, Edmunds PN. 1955. Non-flagellar filamentous appendages (fimbriae) and haemagglutinating activity in Bacterium coli. J Pathol Bacteriol 70:335–348.
6. Brinton CC Jr. 1959. Non-flagellar appendages of bacteria. Nature 183:782–786.
7. Berry JL, Pelicic V. 2015. Exceptionally widespread nanomachines composed of type IV pilins: the prokaryotic Swiss Army knives. FEMS Microbiol Rev 39:134–154.
8. Brinton CC Jr. 1965. The structure, function, synthesis and genetic control of bacterial pili and a molecular model for DNA and RNA transport in gram negative bacteria. Trans N Y Acad Sci 27(8 Series II):1003–1054.
9. Duguid JP. 1959. Fimbriae and adhesive properties in Klebsiella strains. J Gen Microbiol 21:271–286.
10. Kallenius G, Mollby R, Svenson SB, Windberg J, Lundblud A, Svenson S, Cedergen B. 1980. The Pk antigen as receptor for the haemagglutinin of pyelonephritogenic Escherichia coli. FEMS Microbiol Lett 7:297–302.
11. Leffler H, Svanborg-Edén C. 1981. Glycolipid receptors for uropathogenic Escherichia coli on human erythrocytes and uroepithelial cells. Infect Immun 34:920–929.
12. Nowicki B, Labigne A, Moseley S, Hull R, Hull S, Moulds J. 1990. The Dr hemagglutinin, afimbrial adhesins AFA-I and AFA-III, and F1845 fimbriae of uropathogenic and diarrhea-associated Escherichia coli belong to a family of hemagglutinins with Dr receptor recognition. Infect Immun 58:279–281.
13. Nowicki B, Hart A, Coyne KE, Lublin DM, Nowicki S. 1993. Short consensus repeat-3 domain of recombinant decay-accelerating factor is recognized by Escherichia coli recombinant Dr adhesin in a model of a cell-cell interaction. J Exp Med 178:2115–2121.
14. Duguid JP, Anderson ES, Campbell I. 1966. Fimbriae and adhesive properties in Salmonellae. J Pathol Bacteriol 92:107–138.
15. Kisiela D, Sapeta A, Kuczkowski M, Stefaniak T, Wieliczko A, Ugorski M. 2005. Characterization of FimH adhesins expressed by Salmonella enterica serovar Gallinarum biovars Gallinarum and Pullorum: reconstitution of mannose-binding properties by single amino acid substitution. Infect Immun 73:6187–6190.
16. Blattner FR, Plunkett G III, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, Gregor J, Davis NW, Kirkpatrick HA, Goeden MA, Rose DJ, Mau B, Shao Y. 1997. The complete genome sequence of Escherichia coli K-12. Science 277:1453–1462.
17. McClelland M, Sanderson KE, Spieth J, Clifton SW, Latreille P, Courtney L, Porwollik S, Ali J, Dante M, Du F, Hou S, Layman D, Leonard S, Nguyen C, Scott K, Holmes A, Grewal N, Mulvaney E, Ryan E, Sun H, Florea L, Miller W, Stoneking T, Nhan M, Waterston R, Wilson RK. 2001. Complete genome sequence of Salmonella enterica serovar Typhimurium LT2. Nature 413:852–856.
18. Orskov I, Orskov F. 1990. Serologic classification of fimbriae. Curr Top Microbiol Immunol 151:71–90.
19. Piatek R, Zalewska B, Bury K, Kur J. 2005. The chaperone-usher pathway of bacterial adhesin biogenesis -- from molecular mechanism to strategies of anti-bacterial prevention and modern vaccine design. Acta Biochim Pol 52:639–646.
20. Zavialov A, Zav’yalova G, Korpela T, Zav’yalov V. 2007. FGL chaperone-assembled fimbrial polyadhesins: anti-immune armament of Gram-negative bacterial pathogens. FEMS Microbiol Rev 31:478–514.
21. Zav’yalov V, Zavialov A, Zav’yalova G, Korpela T. 2010. Adhesive organelles of Gram-negative pathogens assembled with the classical chaperone/usher machinery: structure and function from a clinical standpoint. FEMS Microbiol Rev 34:317–378.
22. Ilangovan A, Connery S, Waksman G. 2015. Structural biology of the Gram-negative bacterial conjugation systems. Trends Microbiol 23:301–310.
23. Evans ML, Chapman MR. 2014. Curli biogenesis: order out of disorder. Biochim Biophys Acta 1843:1551–1558.
24. Craig L, Li J. 2008. Type IV pili: paradoxes in form and function. Curr Opin Struct Biol 18:267–277.
25. Pelicic V. 2008. Type IV pili: e pluribus unum? Mol Microbiol 68:827–837.
26. Arutyunov D, Frost LS. 2013. F conjugation: back to the beginning. Plasmid 70:18–32.
27. Thanassi DG, Saulino ET, Hultgren SJ. 1998. The chaperone/usher pathway: a major terminal branch of the general secretory pathway. Curr Opin Microbiol 1:223–231.
28. Geibel S, Waksman G. 2014. The molecular dissection of the chaperone-usher pathway. Biochim Biophys Acta 1843:1559–1567.
29. Nuccio SP, Bäumler AJ. 2007. Evolution of the chaperone/usher assembly pathway: fimbrial classification goes Greek. Microbiol Mol Biol Rev 71:551–575.
30. Sakellaris H, Scott JR. 1998. New tools in an old trade: CS1 pilus morphogenesis. Mol Microbiol 30:681–687.
31. Anantha RP, McVeigh AL, Lee LH, Agnew MK, Cassels FJ, Scott DA, Whittam TS, Savarino SJ. 2004. Evolutionary and functional relationships of colonization factor antigen i and other class 5 adhesive fimbriae of enterotoxigenic Escherichia coli. Infect Immun 72:7190–7201.
32. Altboum Z, Levine MM, Galen JE, Barry EM. 2003. Genetic characterization and immunogenicity of coli surface antigen 4 from enterotoxigenic Escherichia coli when it is expressed in a Shigella live-vector strain. Infect Immun 71:1352–1360.
33. Froehlich BJ, Karakashian A, Sakellaris H, Scott JR. 1995. Genes for CS2 pili of enterotoxigenic Escherichia coli and their interchangeability with those for CS1 pili. Infect Immun 63:4849–4856.
34. Hamers AM, Pel HJ, Willshaw GA, Kusters JG, van der Zeijst BA, Gaastra W. 1989. The nucleotide sequence of the first two genes of the CFA/I fimbrial operon of human enterotoxigenic Escherichia coli. Microb Pathog 6:297–309.
35. Froehlich B, Husmann L, Caron J, Scott JR. 1994. Regulation of rns, a positive regulatory factor for pili of enterotoxigenic Escherichia coli. J Bacteriol 176:5385–5392.
36. Folkesson A, Advani A, Sukupolvi S, Pfeifer JD, Normark S, Löfdahl S. 1999. Multiple insertions of fimbrial operons correlate with the evolution of Salmonella serovars responsible for human disease. Mol Microbiol 33:612–622.
37. Low D.B. B, van der Woude M. 1996. Escherichia coli and Salmonella: Cellular and Molecular Biology, 2nd ed. ASM Press, Washington, DC.
38. Zav’yalov VP, Chernovskaya TV, Navolotskaya EV, Karlyshev AV, MacIntyre S, Vasiliev AM, Abramov VM. 1995. Specific high affinity binding of human interleukin 1 beta by Caf1A usher protein of Yersinia pestis. FEBS Lett 371:65–68.
39. Kennan RM, Dhungyel OP, Whittington RJ, Egerton JR, Rood JI. 2001. The type IV fimbrial subunit gene (fimA) of Dichelobacter nodosus is essential for virulence, protease secretion, and natural competence. J Bacteriol 183:4451–4458.
40. Hung DL, Knight SD, Woods RM, Pinkner JS, Hultgren SJ. 1996. Molecular basis of two subfamilies of immunoglobulin-like chaperones. EMBO J 15:3792–3805.
41. Marklund BI, Tennent JM, Garcia E, Hamers A, Båga M, Lindberg F, Gaastra W, Normark S. 1992. Horizontal gene transfer of the Escherichia coli pap and prs pili operons as a mechanism for the development of tissue-specific adhesive properties. Mol Microbiol 6:2225–2242.
42. Abraham SN, Sun D, Dale JB, Beachey EH. 1988. Conservation of the D-mannose-adhesion protein among type 1 fimbriated members of the family Enterobacteriaceae. Nature 336:682–684.
43. Flores-Mireles AL, Walker JN, Caparon M, Hultgren SJ. 2015. Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nat Rev Microbiol 13:269–284.
44. Stamm WE, Norrby SR. 2001. Urinary tract infections: disease panorama and challenges. J Infect Dis 183(Suppl 1):S1–S4.
45. Foxman B. 2010. The epidemiology of urinary tract infection. Nat Rev Urol 7:653–660.
46. Oelschlaeger TA, Dobrindt U, Hacker J. 2002. Virulence factors of uropathogens. Curr Opin Urol 12:33–38.
47. Wurpel DJ, Beatson SA, Totsika M, Petty NK, Schembri MA. 2013. Chaperone-usher fimbriae of Escherichia coli. PLoS One 8:e52835. doi:10.1371/journal.pone.0052835.
48. Korea CG, Badouraly R, Prevost MC, Ghigo JM, Beloin C. 2010. Escherichia coli K-12 possesses multiple cryptic but functional chaperone-usher fimbriae with distinct surface specificities. Environ Microbiol 12:1957–1977.
49. Townsend SM, Kramer NE, Edwards R, Baker S, Hamlin N, Simmonds M, Stevens K, Maloy S, Parkhill J, Dougan G, Bäumler AJ. 2001. Salmonella enterica serovar Typhi possesses a unique repertoire of fimbrial gene sequences. Infect Immun 69:2894–2901.
50. Humphries A, Deridder S, Bäumler AJ. 2005. Salmonella enterica serotype Typhimurium fimbrial proteins serve as antigens during infection of mice. Infect Immun 73:5329–5338.
51. McClelland M, Sanderson KE, Clifton SW, Latreille P, Porwollik S, Sabo A, Meyer R, Bieri T, Ozersky P, McLellan M, Harkins CR, Wang C, Nguyen C, Berghoff A, Elliott G, Kohlberg S, Strong C, Du F, Carter J, Kremizki C, Layman D, Leonard S, Sun H, Fulton L, Nash W, Miner T, Minx P, Delehaunty K, Fronick C, Magrini V, Nhan M, Warren W, Florea L, Spieth J, Wilson RK. 2004. Comparison of genome degradation in Paratyphi A and Typhi, human-restricted serovars of Salmonella enterica that cause typhoid. Nat Genet 36:1268–1274.
52. Parkhill J, Dougan G, James KD, Thomson NR, Pickard D, Wain J, Churcher C, Mungall KL, Bentley SD, Holden MT, Sebaihia M, Baker S, Basham D, Brooks K, Chillingworth T, Connerton P, Cronin A, Davis P, Davies RM, Dowd L, White N, Farrar J, Feltwell T, Hamlin N, Haque A, Hien TT, Holroyd S, Jagels K, Krogh A, Larsen TS, Leather S, Moule S, O’Gaora P, Parry C, Quail M, Rutherford K, Simmonds M, Skelton J, Stevens K, Whitehead S, Barrell BG. 2001. Complete genome sequence of a multiple drug resistant Salmonella enterica serovar Typhi CT18. Nature 413:848–852.
53. Weissman SJ, Chattopadhyay S, Aprikian P, Obata-Yasuoka M, Yarova-Yarovaya Y, Stapleton A, Ba-Thein W, Dykhuizen D, Johnson JR, Sokurenko EV. 2006. Clonal analysis reveals high rate of structural mutations in fimbrial adhesins of extraintestinal pathogenic Escherichia coli. Mol Microbiol 59:975–988.
54. Schwartz DJ, Kalas V, Pinkner JS, Chen SL, Spaulding CN, Dodson KW, Hultgren SJ. 2013. Positively selected FimH residues enhance virulence during urinary tract infection by altering FimH conformation. Proc Natl Acad Sci USA 110:15530–15537.
55. Sokurenko EV, Chesnokova V, Doyle RJ, Hasty DL. 1997. Diversity of the Escherichia coli type 1 fimbrial lectin. Differential binding to mannosides and uroepithelial cells. J Biol Chem 272:17880–17886.
56. Clegg S, Wilson J, Johnson J. 2011. More than one way to control hair growth: regulatory mechanisms in enterobacteria that affect fimbriae assembled by the chaperone/usher pathway. J Bacteriol 193:2081–2088.
57. Blomfield IC. 2001. The regulation of pap and type 1 fimbriation in Escherichia coli. Adv Microb Physiol 45:1–49.
58. van der Woude M, Braaten B, Low D. 1996. Epigenetic phase variation of the pap operon in Escherichia coli. Trends Microbiol 4:5–9.
59. Schwan WR. 2011. Regulation of fim genes in uropathogenic Escherichia coli. World J Clin Infect Dis 1:17–25.
60. Xia Y, Gally D, Forsman-Semb K, Uhlin BE. 2000. Regulatory cross-talk between adhesin operons in Escherichia coli: inhibition of type 1 fimbriae expression by the PapB protein. EMBO J 19:1450–1457.
61. Totsika M, Beatson SA, Holden N, Gally DL. 2008. Regulatory interplay between pap operons in uropathogenic Escherichia coli. Mol Microbiol 67:996–1011.
62. Snyder JA, Haugen BJ, Lockatell CV, Maroncle N, Hagan EC, Johnson DE, Welch RA, Mobley HL. 2005. Coordinate expression of fimbriae in uropathogenic Escherichia coli. Infect Immun 73:7588–7596.
63. Holden NJ, Totsika M, Mahler E, Roe AJ, Catherwood K, Lindner K, Dobrindt U, Gally DL. 2006. Demonstration of regulatory cross-talk between P fimbriae and type 1 fimbriae in uropathogenic Escherichia coli. Microbiology 152:1143–1153.
64. Lane MC, Simms AN, Mobley HLT. 2007. complex interplay between type 1 fimbrial expression and flagellum-mediated motility of uropathogenic Escherichia coli. J Bacteriol 189:5523–5533.
65. Gally DL, Leathart J, Blomfield IC. 1996. Interaction of FimB and FimE with the fim switch that controls the phase variation of type 1 fimbriae in Escherichia coli K-12. Mol Microbiol 21:725–738.
66. Olsen PB, Klemm P. 1994. Localization of promoters in the fim gene cluster and the effect of H-NS on the transcription of fimB and fimE. FEMS Microbiol Lett 116:95–100.
67. Aberg A, Shingler V, Balsalobre C. 2008. Regulation of the fimB promoter: a case of differential regulation by ppGpp and DksA in vivo. Mol Microbiol 67:1223–1241.
68. Adiciptaningrum AM, Blomfield IC, Tans SJ. 2009. Direct observation of type 1 fimbrial switching. EMBO Rep 10:527–532.
69. Eisenstein BI. 1981. Phase variation of type 1 fimbriae in Escherichia coli is under transcriptional control. Science 214:337–339.
70. Orndorff PE, Spears PA, Schauer D, Falkow S. 1985. Two modes of control of pilA, the gene encoding type 1 pilin in Escherichia coli. J Bacteriol 164:321–330.
71. Wu Y, Outten FW. 2009. IscR controls iron-dependent biofilm formation in Escherichia coli by regulating type I fimbria expression. J Bacteriol 191:1248–1257.
72. Aberg A, Shingler V, Balsalobre C. 2006. (p)ppGpp regulates type 1 fimbriation of Escherichia coli by modulating the expression of the site-specific recombinase FimB. Mol Microbiol 60:1520–1533.
73. Holden NJ, Uhlin BE, Gally DL. 2001. PapB paralogues and their effect on the phase variation of type 1 fimbriae in Escherichia coli. Mol Microbiol 42:319–330.
74. Sjöström AE, Sondén B, Müller C, Rydström A, Dobrindt U, Wai SN, Uhlin BE. 2009. Analysis of the sfaX(II) locus in the Escherichia coli meningitis isolate IHE3034 reveals two novel regulatory genes within the promoter-distal region of the main S fimbrial operon. Microb Pathog 46:150–158.
75. Corcoran CP, Dorman CJ. 2009. DNA relaxation-dependent phase biasing of the fim genetic switch in Escherichia coli depends on the interplay of H-NS, IHF and LRP. Mol Microbiol 74:1071–1082.
76. Holden N, Blomfield IC, Uhlin BE, Totsika M, Kulasekara DH, Gally DL. 2007. Comparative analysis of FimB and FimE recombinase activity. Microbiology 153:4138–4149.
77. Old DC, Duguid JP. 1970. Selective outgrowth of fimbriate bacteria in static liquid medium. J Bacteriol 103:447–456.
78. Schwan WR, Lee JL, Lenard FA, Matthews BT, Beck MT. 2002. Osmolarity and pH growth conditions regulate fim gene transcription and type 1 pilus expression in uropathogenic Escherichia coli. Infect Immun 70:1391–1402.
79. Floyd KA, Moore JL, Eberly AR, Good JA, Shaffer CL, Zaver H, Almqvist F, Skaar EP, Caprioli RM, Hadjifrangiskou M. 2015. Adhesive fiber stratification in uropathogenic Escherichia coli biofilms unveils oxygen-mediated control of type 1 pili. PLoS Pathog 11:e1004697. doi:10.1371/journal.ppat.1004697.
80. Floyd KA, Mitchell CA, Eberly AR, Colling SJ, Zhang EW, DePas W, Chapman MR, Conover M, Rogers BR, Hultgren SJ, Hadjifrangiskou M. 2016. The UbiI (VisC) aerobic ubiquinone synthase Is required for expression of type 1 pili, biofilm formation, and pathogenesis in uropathogenic Escherichia coli. J Bacteriol 198:2662–2672.
81. van der Woude MW, Bäumler AJ. 2004. Phase and antigenic variation in bacteria. Clin Microbiol Rev 17:581–611.
82. Braaten BA, Blyn LB, Skinner BS, Low DA. 1991. Evidence for a methylation-blocking factor (mbf) locus involved in pap pilus expression and phase variation in Escherichia coli. J Bacteriol 173:1789–1800.
83. Peterson SN, Reich NO. 2008. Competitive Lrp and Dam assembly at the pap regulatory region: implications for mechanisms of epigenetic regulation. J Mol Biol 383:92–105.
84. Peterson SN, Reich NO. 2006. GATC flanking sequences regulate Dam activity: evidence for how Dam specificity may influence pap expression. J Mol Biol 355:459–472.
85. Nou X, Braaten B, Kaltenbach L, Low DA. 1995. Differential binding of Lrp to two sets of pap DNA binding sites mediated by Pap I regulates Pap phase variation in Escherichia coli. EMBO J 14:5785–5797.
86. Forsman K, Göransson M, Uhlin BE. 1989. Autoregulation and multiple DNA interactions by a transcriptional regulatory protein in E. coli pili biogenesis. EMBO J 8:1271–1277.
87. Holden N, Totsika M, Dixon L, Catherwood K, Gally DL. 2007. Regulation of P-fimbrial phase variation frequencies in Escherichia coli CFT073. Infect Immun 75:3325–3334.
88. Hernday AD, Braaten BA, Broitman-Maduro G, Engelberts P, Low DA. 2004. Regulation of the pap epigenetic switch by CpxAR: phosphorylated CpxR inhibits transition to the phase ON state by competition with Lrp. Mol Cell 16:537–547.
89. Khandige S, Kronborg T, Uhlin BE, Møller-Jensen J. 2015. sRNA-mediated regulation of P-fimbriae phase variation in uropathogenic Escherichia coli. PLoS Pathog 11:e1005109. doi:10.1371/journal.ppat.1005109.
90. Servin AL. 2005. Pathogenesis of Afa/Dr diffusely adhering Escherichia coli. Clin Microbiol Rev 18:264–292.
91. Nowicki B, Selvarangan R, Nowicki S. 2001. Family of Escherichia coli Dr adhesins: decay-accelerating factor receptor recognition and invasiveness. J Infect Dis 183(Suppl 1):S24–S27.
92. Båga M, Norgren M, Normark S. 1987. Biogenesis of E. coli Pap pili: papH, a minor pilin subunit involved in cell anchoring and length modulation. Cell 49:241–251.
93. Rossolini GM, Muscas P, Chiesurin A, Satta G. 1993. Analysis of the Salmonella fim gene cluster: identification of a new gene (fimI) encoding a fimbrin-like protein and located downstream from the fimA gene. FEMS Microbiol Lett 114:259–265.
94. Valenski ML, Harris SL, Spears PA, Horton JR, Orndorff PE. 2003. The Product of the fimI gene is necessary for Escherichia coli type 1 pilus biosynthesis. J Bacteriol 185:5007–5011.
95. Garcia MI, Gounon P, Courcoux P, Labigne A, Le Bouguenec C. 1996. The afimbrial adhesive sheath encoded by the afa-3 gene cluster of pathogenic Escherichia coli is composed of two adhesins. Mol Microbiol 19:683–693.
96. Labigne-Roussel AF, Lark D, Schoolnik G, Falkow S. 1984. Cloning and expression of an afimbrial adhesin (AFA-I) responsible for P blood group-independent, mannose-resistant hemagglutination from a pyelonephritic Escherichia coli strain. Infect Immun 46:251–259.
97. Labigne-Roussel AF, Schmidt MA, Walz W, Falkow S. 1985. Genetic organization of the AFA operon and nucleotide sequence from a uropathogenic Escherichia coli gene encoding an afimbrial adhesin (AFA-1). J Bacteriol 162:1285–1292.
98. Walz W, Schmidt MA, Labigne-Roussel AF, Falkow S, Schoolnik G. 1985. AFA-I, a cloned afimbrial X-type adhesin from a human pyelonephritic Escherichia coli strain. Purification and chemical, functional and serologic characterization. Eur J Biochem 152:315–321.
99. Anderson KL, Billington J, Pettigrew D, Cota E, Simpson P, Roversi P, Chen HA, Urvil P, du Merle L, Barlow PN, Medof ME, Smith RA, Nowicki B, Le Bouguénec C, Lea SM, Matthews S. 2004. An atomic resolution model for assembly, architecture, and function of the Dr adhesins. Mol Cell 15:647–657.
100. Jouve M, Garcia MI, Courcoux P, Labigne A, Gounon P, Le Bouguénec C. 1997. Adhesion to and invasion of HeLa cells by pathogenic Escherichia coli carrying the afa-3 gene cluster are mediated by the AfaE and AfaD proteins, respectively. Infect Immun 65:4082–4089.
101. Gounon P, Jouve M, Le Bouguénec C. 2000. Immunocytochemistry of the AfaE adhesin and AfaD invasin produced by pathogenic Escherichia coli strains during interaction of the bacteria with HeLa cells by high-resolution scanning electron microscopy. Microbes Infect 2:359–365.
102. Zalewska B, Piatek R, Bury K, Samet A, Nowicki B, Nowicki S, Kur J. 2005. A surface-exposed DraD protein of uropathogenic Escherichia coli bearing Dr fimbriae may be expressed and secreted independently from DraC usher and DraE adhesin. Microbiology 151:2477–2486.
103. Pettigrew D, Anderson KL, Billington J, Cota E, Simpson P, Urvil P, Rabuzin F, Roversi P, Nowicki B, du Merle L, Le Bouguénec C, Matthews S, Lea SM. 2004. High resolution studies of the Afa/Dr adhesin DraE and its interaction with chloramphenicol. J Biol Chem 279:46851–46857.
104. Korotkova N, Le Trong I, Samudrala R, Korotkov K, Van Loy CP, Bui AL, Moseley SL, Stenkamp RE. 2006. Crystal structure and mutational analysis of the DaaE adhesin of Escherichia coli. J Biol Chem 281:22367–22377.
105. Bork P, Holm L, Sander C. 1994. The immunoglobulin fold. Structural classification, sequence patterns and common core. J Mol Biol 242:309–320.
106. Choudhury D, Thompson A, Stojanoff V, Langermann S, Pinkner J, Hultgren SJ, Knight SD. 1999. X-ray structure of the FimC-FimH chaperone-adhesin complex from uropathogenic Escherichia coli. Science 285:1061–1066.
107. Sauer FG, Fütterer K, Pinkner JS, Dodson KW, Hultgren SJ, Waksman G. 1999. Structural basis of chaperone function and pilus biogenesis. Science 285:1058–1061.
108. Sauer FG, Pinkner JS, Waksman G, Hultgren SJ. 2002. Chaperone priming of pilus subunits facilitates a topological transition that drives fiber formation. Cell 111:543–551.
109. Zavialov AV, Berglund J, Pudney AF, Fooks LJ, Ibrahim TM, MacIntyre S, Knight SD. 2003. Structure and biogenesis of the capsular F1 antigen from Yersinia pestis: preserved folding energy drives fiber formation. Cell 113:587–596.
110. Westerlund-Wikström B, Korhonen TK. 2005. Molecular structure of adhesin domains in Escherichia coli fimbriae. Int J Med Microbiol 295:479–486.
111. Hung CS, Bouckaert J, Hung D, Pinkner J, Widberg C, DeFusco A, Auguste CG, Strouse R, Langermann S, Waksman G, Hultgren SJ. 2002. Structural basis of tropism of Escherichia coli to the bladder during urinary tract infection. Mol Microbiol 44:903–915.
112. Dodson KW, Pinkner JS, Rose T, Magnusson G, Hultgren SJ, Waksman G. 2001. Structural basis of the interaction of the pyelonephritic E. coli adhesin to its human kidney receptor. Cell 105:733–743.
113. Sung MA, Chen HA, Matthews S. 2001. Sequential assignment and secondary structure of the triple-labelled carbohydrate-binding domain of papG from uropathogenic E. coli. J Biomol NMR 19:197–198.
114. Piątek R, Bruździak P, Wojciechowski M, Zalewska-Piątek B, Kur J. 2010. The noncanonical disulfide bond as the important stabilizing element of the immunoglobulin fold of the Dr fimbrial DraE subunit. Biochemistry 49:1460–1468.
115. Thomas WE, Trintchina E, Forero M, Vogel V, Sokurenko EV. 2002. Bacterial adhesion to target cells enhanced by shear force. Cell 109:913–923.
116. Thomas WE, Nilsson LM, Forero M, Sokurenko EV, Vogel V. 2004. Shear-dependent ‘stick-and-roll’ adhesion of type 1 fimbriated Escherichia coli. Mol Microbiol 53:1545–1557.
117. Geibel S, Procko E, Hultgren SJ, Baker D, Waksman G. 2013. Structural and energetic basis of folded-protein transport by the FimD usher. Nature 496:243–246.
118. Le Trong I, Aprikian P, Kidd BA, Forero-Shelton M, Tchesnokova V, Rajagopal P, Rodriguez V, Interlandi G, Klevit R, Vogel V, Stenkamp RE, Sokurenko EV, Thomas WE. 2010. Structural basis for mechanical force regulation of the adhesin FimH via finger trap-like beta sheet twisting. Cell 141:645–655.
119. Sauer MM, Jakob RP, Eras J, Baday S, Eriş D, Navarra G, Bernèche S, Ernst B, Maier T, Glockshuber R. 2016. Catch-bond mechanism of the bacterial adhesin FimH. Nat Commun 7:10738. doi:10.1038/ncomms10738.
120. Yakovenko O, Tchesnokova V, Sokurenko EV, Thomas WE. 2015. Inactive conformation enhances binding function in physiological conditions. Proc Natl Acad Sci USA 112:9884–9889.
121. Pak J, Pu Y, Zhang ZT, Hasty DL, Wu XR. 2001. Tamm-Horsfall protein binds to type 1 fimbriated Escherichia coli and prevents E. coli from binding to uroplakin Ia and Ib receptors. J Biol Chem 276:9924–9930.
122. Lugmaier RA, Schedin S, Kühner F, Benoit M. 2008. Dynamic restacking of Escherichia coli P-pili. Eur Biophys J 37:111–120.
123. Larsson A, Ohlsson J, Dodson KW, Hultgren SJ, Nilsson U, Kihlberg J. 2003. Quantitative studies of the binding of the class II PapG adhesin from uropathogenic Escherichia coli to oligosaccharides. Bioorg Med Chem 11:2255–2261.
124. Zakrisson J, Wiklund K, Axner O, Andersson M. 2013. The shaft of the type 1 fimbriae regulates an external force to match the FimH catch bond. Biophys J 104:2137–2148.
125. Jass J, Schedin S, Fällman E, Ohlsson J, Nilsson UJ, Uhlin BE, Axner O. 2004. Physical properties of Escherichia coli P pili measured by optical tweezers. Biophys J 87:4271–4283.
126. Andersson M, Axner O, Almqvist F, Uhlin BE, Fällman E. 2008. Physical properties of biopolymers assessed by optical tweezers: analysis of folding and refolding of bacterial pili. ChemPhysChem 9:221–235.
127. Fällman E, Schedin S, Jass J, Uhlin BE, Axner O. 2005. The unfolding of the P pili quaternary structure by stretching is reversible, not plastic. EMBO Rep 6:52–56.
128. Hospenthal MK, Redzej A, Dodson K, Ukleja M, Frenz B, Rodrigues C, Hultgren SJ, DiMaio F, Egelman EH, Waksman G. 2016. Structure of a chaperone-usher pilus reveals the molecular basis of rod uncoiling. Cell 164:269–278.
129. Mortezaei N, Singh B, Zakrisson J, Bullitt E, Andersson M. 2015. Biomechanical and structural features of CS2 fimbriae of enterotoxigenic Escherichia coli. Biophys J 109:49–56.
130. Jacob-Dubuisson F, Striker R, Hultgren SJ. 1994. Chaperone-assisted self-assembly of pili independent of cellular energy. J Biol Chem 269:12447–12455.
131. Thanassi DG, Stathopoulos C, Karkal A, Li H. 2005. Protein secretion in the absence of ATP: the autotransporter, two-partner secretion and chaperone/usher pathways of gram-negative bacteria (review). Mol Membr Biol 22:63–72.
132. Lycklama A Nijeholt JA, Driessen AJ, Driessen AJ. 2012. The bacterial Sec-translocase: structure and mechanism. Philos Trans R Soc Lond B Biol Sci 367:1016–1028.
133. Totsika M, Heras B, Wurpel DJ, Schembri MA. 2009. Characterization of two homologous disulfide bond systems involved in virulence factor biogenesis in uropathogenic Escherichia coli CFT073. J Bacteriol 191:3901–3908.
134. Crespo MD, Puorger C, Schärer MA, Eidam O, Grütter MG, Capitani G, Glockshuber R. 2012. Quality control of disulfide bond formation in pilus subunits by the chaperone FimC. Nat Chem Biol 8:707–713.
135. Waksman G, Hultgren SJ. 2009. Structural biology of the chaperone-usher pathway of pilus biogenesis. Nat Rev Microbiol 7:765–774.
136. Zavialov AV, Tischenko VM, Fooks LJ, Brandsdal BO, Aqvist J, Zav’yalov VP, Macintyre S, Knight SD. 2005. Resolving the energy paradox of chaperone/usher-mediated fibre assembly. Biochem J 389:685–694.
137. Nishiyama M, Vetsch M, Puorger C, Jelesarov I, Glockshuber R. 2003. Identification and characterization of the chaperone-subunit complex-binding domain from the type 1 pilus assembly platform FimD. J Mol Biol 330:513–525.
138. Bann JG, Pinkner JS, Frieden C, Hultgren SJ. 2004. Catalysis of protein folding by chaperones in pathogenic bacteria. Proc Natl Acad Sci USA 101:17389–17393.
139. Zav’yalov VP, Chernovskaya TV, Chapman DA, Karlyshev AV, MacIntyre S, Zavialov AV, Vasiliev AM, Denesyuk AI, Zav’yalova GA, Dudich IV, Korpela T, Abramov VM. 1997. Influence of the conserved disulphide bond, exposed to the putative binding pocket, on the structure and function of the immunoglobulin-like molecular chaperone Caf1M of Yersinia pestis. Biochem J 324:571–578.
140. Eidam O, Dworkowski FS, Glockshuber R, Grütter MG, Capitani G. 2008. Crystal structure of the ternary FimC-FimF(t)-FimD(N) complex indicates conserved pilus chaperone-subunit complex recognition by the usher FimD. FEBS Lett 582:651–655.
141. Verger D, Bullitt E, Hultgren SJ, Waksman G. 2007. Crystal structure of the P pilus rod subunit PapA. PLoS Pathog 3:e73. doi:10.1371/journal.ppat.0030073.
142. Verger D, Miller E, Remaut H, Waksman G, Hultgren S. 2006. Molecular mechanism of P pilus termination in uropathogenic Escherichia coli. EMBO Rep 7:1228–1232.
143. Verger D, Rose RJ, Paci E, Costakes G, Daviter T, Hultgren S, Remaut H, Ashcroft AE, Radford SE, Waksman G. 2008. Structural determinants of polymerization reactivity of the P pilus adaptor subunit PapF. Structure 16:1724–1731.
144. Ford B, Verger D, Dodson K, Volkan E, Kostakioti M, Elam J, Pinkner J, Waksman G, Hultgren S. 2012. The structure of the PapD-PapGII pilin complex reveals an open and flexible P5 pocket. J Bacteriol 194:6390–6397.
145. Yu XD, Fooks LJ, Moslehi-Mohebi E, Tischenko VM, Askarieh G, Knight SD, Macintyre S, Zavialov AV. 2012. Large is fast, small is tight: determinants of speed and affinity in subunit capture by a periplasmic chaperone. J Mol Biol 417:294–308.
146. Remaut H, Rose RJ, Hannan TJ, Hultgren SJ, Radford SE, Ashcroft AE, Waksman G. 2006. Donor-strand exchange in chaperone-assisted pilus assembly proceeds through a concerted beta strand displacement mechanism. Mol Cell 22:831–842.
147. Piątek R, Zalewska B, Kolaj O, Ferens M, Nowicki B, Kur J. 2005. Molecular aspects of biogenesis of Escherichia coli Dr Fimbriae: characterization of DraB-DraE complexes. Infect Immun 73:135–145.
148. Puorger C, Eidam O, Capitani G, Erilov D, Grütter MG, Glockshuber R. 2008. Infinite kinetic stability against dissociation of supramolecular protein complexes through donor strand complementation. Structure 16:631–642.
149. Nishiyama M, Ishikawa T, Rechsteiner H, Glockshuber R. 2008. Reconstitution of pilus assembly reveals a bacterial outer membrane catalyst. Science 320:376–379.
150. Nishiyama M, Horst R, Eidam O, Herrmann T, Ignatov O, Vetsch M, Bettendorff P, Jelesarov I, Grütter MG, Wüthrich K, Glockshuber R, Capitani G. 2005. Structural basis of chaperone-subunit complex recognition by the type 1 pilus assembly platform FimD. EMBO J 24:2075–2086.
151. Phan G, Remaut H, Wang T, Allen WJ, Pirker KF, Lebedev A, Henderson NS, Geibel S, Volkan E, Yan J, Kunze MB, Pinkner JS, Ford B, Kay CW, Li H, Hultgren SJ, Thanassi DG, Waksman G. 2011. Crystal structure of the FimD usher bound to its cognate FimC-FimH substrate. Nature 474:49–53.
152. Remaut H, Tang C, Henderson NS, Pinkner JS, Wang T, Hultgren SJ, Thanassi DG, Waksman G, Li H. 2008. Fiber formation across the bacterial outer membrane by the chaperone/usher pathway. Cell 133:640–652.
153. Huang Y, Smith BS, Chen LX, Baxter RH, Deisenhofer J. 2009. Insights into pilus assembly and secretion from the structure and functional characterization of usher PapC. Proc Natl Acad Sci USA 106:7403–7407.
154. Di Yu X, Dubnovitsky A, Pudney AF, Macintyre S, Knight SD, Zavialov AV. 2012. Allosteric mechanism controls traffic in the chaperone/usher pathway. Structure 20:1861–1871.
155. Werneburg GT, Henderson NS, Portnoy EB, Sarowar S, Hultgren SJ, Li H, Thanassi DG. 2015. The pilus usher controls protein interactions via domain masking and is functional as an oligomer. Nat Struct Mol Biol 22:540–546.
156. Volkan E, Ford BA, Pinkner JS, Dodson KW, Henderson NS, Thanassi DG, Waksman G, Hultgren SJ. 2012. Domain activities of PapC usher reveal the mechanism of action of an Escherichia coli molecular machine. Proc Natl Acad Sci USA 109:9563–9568.
157. Thanassi DG, Saulino ET, Lombardo MJ, Roth R, Heuser J, Hultgren SJ. 1998. The PapC usher forms an oligomeric channel: implications for pilus biogenesis across the outer membrane. Proc Natl Acad Sci USA 95:3146–3151.
158. Li H, Qian L, Chen Z, Thibault D, Liu G, Liu T, Thanassi DG. 2004. The outer membrane usher forms a twin-pore secretion complex. J Mol Biol 344:1397–1407.
159. So SS, Thanassi DG. 2006. Analysis of the requirements for pilus biogenesis at the outer membrane usher and the function of the usher C-terminus. Mol Microbiol 60:364–375.
160. Nishiyama M, Glockshuber R. 2010. The outer membrane usher guarantees the formation of functional pili by selectively catalyzing donor-strand exchange between subunits that are adjacent in the mature pilus. J Mol Biol 396:1–8.
161. Li Q, Ng TW, Dodson KW, So SS, Bayle KM, Pinkner JS, Scarlata S, Hultgren SJ, Thanassi DG. 2010. The differential affinity of the usher for chaperone-subunit complexes is required for assembly of complete pili. Mol Microbiol 76:159–172.
162. Saulino ET, Thanassi DG, Pinkner JS, Hultgren SJ. 1998. Ramifications of kinetic partitioning on usher-mediated pilus biogenesis. EMBO J 17:2177–2185.
163. Allen WJ, Phan G, Hultgren SJ, Waksman G. 2013. Dissection of pilus tip assembly by the FimD usher monomer. J Mol Biol 425:958–967.
164. Durno C, Soni R, Sherman P. 1989. Adherence of vero cytotoxin-producing Escherichia coli serotype O157:H7 to isolated epithelial cells and brush border membranes in vitro: role of type 1 fimbriae (pili) as a bacterial adhesin expressed by strain CL-49. Clin Invest Med 12:194–200.
165. Sherman P, Soni R, Petric M, Karmali M. 1987. Surface properties of the Vero cytotoxin-producing Escherichia coli O157:H7. Infect Immun 55:1824–1829.
166. Kim SH, Kim YH. 2004. Escherichia coli O157:H7 adherence to HEp-2 cells is implicated with curli expression and outer membrane integrity. J Vet Sci 5:119–124.
167. Brunder W, Khan AS, Hacker J, Karch H. 2001. Novel type of fimbriae encoded by the large plasmid of sorbitol-fermenting enterohemorrhagic Escherichia coli O157:H(-). Infect Immun 69:4447–4457.
168. Karch H, Heesemann J, Laufs R, O’Brien AD, Tacket CO, Levine MM. 1987. A plasmid of enterohemorrhagic Escherichia coli O157:H7 is required for expression of a new fimbrial antigen and for adhesion to epithelial cells. Infect Immun 55:455–461.
169. Hayashi T, Makino K, Ohnishi M, Kurokawa K, Ishii K, Yokoyama K, Han CG, Ohtsubo E, Nakayama K, Murata T, Tanaka M, Tobe T, Iida T, Takami H, Honda T, Sasakawa C, Ogasawara N, Yasunaga T, Kuhara S, Shiba T, Hattori M, Shinagawa H. 2001. Complete genome sequence of enterohemorrhagic Escherichia coli O157:H7 and genomic comparison with a laboratory strain K-12. DNA Res 8:11–22.
170. Perna NT, Plunkett G III, Burland V, Mau B, Glasner JD, Rose DJ, Mayhew GF, Evans PS, Gregor J, Kirkpatrick HA, Pósfai G, Hackett J, Klink S, Boutin A, Shao Y, Miller L, Grotbeck EJ, Davis NW, Lim A, Dimalanta ET, Potamousis KD, Apodaca J, Anantharaman TS, Lin J, Yen G, Schwartz DC, Welch RA, Blattner FR. 2001. Genome sequence of enterohaemorrhagic Escherichia coli O157:H7. Nature 409:529–533.
171. Low AS, Holden N, Rosser T, Roe AJ, Constantinidou C, Hobman JL, Smith DG, Low JC, Gally DL. 2006. Analysis of fimbrial gene clusters and their expression in enterohaemorrhagic Escherichia coli O157:H7. Environ Microbiol 8:1033–1047.
172. Roe AJ, Currie C, Smith DG, Gally DL. 2001. Analysis of type 1 fimbriae expression in verotoxigenic Escherichia coli: a comparison between serotypes O157 and O26. Microbiology 147:145–152.
173. Dziva F, van Diemen PM, Stevens MP, Smith AJ, Wallis TS. 2004. Identification of Escherichia coli O157 : H7 genes influencing colonization of the bovine gastrointestinal tract using signature-tagged mutagenesis. Microbiology 150:3631–3645.
174. Jordan DM, Cornick N, Torres AG, Dean-Nystrom EA, Kaper JB, Moon HW. 2004. Long polar fimbriae contribute to colonization by Escherichia coli O157:H7 in vivo. Infect Immun 72:6168–6171.
175. Low AS, Dziva F, Torres AG, Martinez JL, Rosser T, Naylor S, Spears K, Holden N, Mahajan A, Findlay J, Sales J, Smith DG, Low JC, Stevens MP, Gally DL. 2006. Cloning, expression, and characterization of fimbrial operon F9 from enterohemorrhagic Escherichia coli O157:H7. Infect Immun 74:2233–2244.
176. Torres AG, Giron JA, Perna NT, Burland V, Blattner FR, Avelino-Flores F, Kaper JB. 2002. Identification and characterization of lpfABCC’DE, a fimbrial operon of enterohemorrhagic Escherichia coli O157:H7. Infect Immun 70:5416–5427.
177. Torres AG, Kanack KJ, Tutt CB, Popov V, Kaper JB. 2004. Characterization of the second long polar (LP) fimbriae of Escherichia coli O157:H7 and distribution of LP fimbriae in other pathogenic E. coli strains. FEMS Microbiol Lett 238:333–344.
178. Zhou G, Mo WJ, Sebbel P, Min G, Neubert TA, Glockshuber R, Wu XR, Sun TT, Kong XP. 2001. Uroplakin Ia is the urothelial receptor for uropathogenic Escherichia coli: evidence from in vitro FimH binding. J Cell Sci 114:4095–4103.
179. Eto DS, Jones TA, Sundsbak JL, Mulvey MA. 2007. Integrin-mediated host cell invasion by type 1-piliated uropathogenic Escherichia coli. PLoS Pathog 3:e100. doi:10.1371/journal.ppat.0030100.
180. Langermann S, Möllby R, Burlein JE, Palaszynski SR, Auguste CG, DeFusco A, Strouse R, Schenerman MA, Hultgren SJ, Pinkner JS, Winberg J, Guldevall L, Söderhäll M, Ishikawa K, Normark S, Koenig S. 2000. Vaccination with FimH adhesin protects cynomolgus monkeys from colonization and infection by uropathogenic Escherichia coli. J Infect Dis 181:774–778.
181. Langermann S, Palaszynski S, Barnhart M, Auguste G, Pinkner JS, Burlein J, Barren P, Koenig S, Leath S, Jones CH, Hultgren SJ. 1997. Prevention of mucosal Escherichia coli infection by FimH-adhesin-based systemic vaccination. Science 276:607–611.
182. Hannan TJ, Totsika M, Mansfield KJ, Moore KH, Schembri MA, Hultgren SJ. 2012. Host-pathogen checkpoints and population bottlenecks in persistent and intracellular uropathogenic Escherichia coli bladder infection. FEMS Microbiol Rev 36:616–648.
183. Pratt LA, Kolter R. 1998. Genetic analysis of Escherichia coli biofilm formation: roles of flagella, motility, chemotaxis and type I pili. Mol Microbiol 30:285–293.
184. Kukkonen M, Raunio T, Virkola R, Lähteenmäki K, Mäkelä PH, Klemm P, Clegg S, Korhonen TK. 1993. Basement membrane carbohydrate as a target for bacterial adhesion: binding of type I fimbriae of Salmonella enterica and Escherichia coli to laminin. Mol Microbiol 7:229–237.
185. Baorto DM, Gao Z, Malaviya R, Dustin ML, van der Merwe A, Lublin DM, Abraham SN. 1997. Survival of FimH-expressing enterobacteria in macrophages relies on glycolipid traffic. Nature 389:636–639.
186. Mulvey MA, Lopez-Boado YS, Wilson CL, Roth R, Parks WC, Heuser J, Hultgren SJ. 1998. Induction and evasion of host defenses by type 1-piliated uropathogenic Escherichia coli. Science 282:1494–1497.
187. Liu Y, Mémet S, Saban R, Kong X, Aprikian P, Sokurenko E, Sun TT, Wu XR. 2015. Dual ligand/receptor interactions activate urothelial defenses against uropathogenic E. coli. Sci Rep 5:16234. doi:10.1038/srep16234.
188. Martinez JJ, Mulvey MA, Schilling JD, Pinkner JS, Hultgren SJ. 2000. Type 1 pilus-mediated bacterial invasion of bladder epithelial cells. EMBO J 19:2803–2812.
189. Keith BR, Harris SL, Russell PW, Orndorff PE. 1990. Effect of type 1 piliation on in vitro killing of Escherichia coli by mouse peritoneal macrophages. Infect Immun 58:3448–3454.
190. Avalos Vizcarra I, Hosseini V, Kollmannsberger P, Meier S, Weber SS, Arnoldini M, Ackermann M, Vogel V. 2016. How type 1 fimbriae help Escherichia coli to evade extracellular antibiotics. Sci Rep 6:18109. doi:10.1038/srep18109.
191. Glasser AL, Boudeau J, Barnich N, Perruchot MH, Colombel JF, Darfeuille-Michaud A. 2001. Adherent invasive Escherichia coli strains from patients with Crohn’s disease survive and replicate within macrophages without inducing host cell death. Infect Immun 69:5529–5537.
192. Sukumaran SK, Fu NY, Tin CB, Wan KF, Lee SS, Yu VC. 2010. A soluble form of the pilus protein FimA targets the VDAC-hexokinase complex at mitochondria to suppress host cell apoptosis. Mol Cell 37:768–783.
193. Walczak MJ, Puorger C, Glockshuber R, Wider G. 2014. Intramolecular donor strand complementation in the E. coli type 1 pilus subunit FimA explains the existence of FimA monomers as off-pathway products of pilus assembly that inhibit host cell apoptosis. J Mol Biol 426:542–549.
194. Wright KJ, Seed PC, Hultgren SJ. 2007. Development of intracellular bacterial communities of uropathogenic Escherichia coli depends on type 1 pili. Cell Microbiol 9:2230–2241.
195. Chen SL, Hung CS, Pinkner JS, Walker JN, Cusumano CK, Li Z, Bouckaert J, Gordon JI, Hultgren SJ. 2009. Positive selection identifies an in vivo role for FimH during urinary tract infection in addition to mannose binding. Proc Natl Acad Sci USA 106:22439–22444.
196. Mulvey MA, Schilling JD, Hultgren SJ. 2001. Establishment of a persistent Escherichia coli reservoir during the acute phase of a bladder infection. Infect Immun 69:4572–4579.
197. Justice SS, Hung C, Theriot JA, Fletcher DA, Anderson GG, Footer MJ, Hultgren SJ. 2004. Differentiation and developmental pathways of uropathogenic Escherichia coli in urinary tract pathogenesis. Proc Natl Acad Sci USA 101:1333–1338.
198. Mysorekar IU, Hultgren SJ. 2006. Mechanisms of uropathogenic Escherichia coli persistence and eradication from the urinary tract. Proc Natl Acad Sci USA 103:14170–14175.
199. Ewers C, Li G, Wilking H, Kiessling S, Alt K, Antáo EM, Laturnus C, Diehl I, Glodde S, Homeier T, Böhnke U, Steinrück H, Philipp HC, Wieler LH. 2007. Avian pathogenic, uropathogenic, and newborn meningitis-causing Escherichia coli: how closely related are they? Int J Med Microbiol 297:163–176.
200. Tennent JM, Lindberg F, Normark S. 1990. Integrity of Escherichia coli P pili during biogenesis: properties and role of PapJ. Mol Microbiol 4:747–758.
201. Roberts JA, Marklund B-I, Ilver D, Haslam D, Kaack MB, Baskin G, Louis M, Möllby R, Winberg J, Normark S. 1994. The Gal(alpha 1-4)Gal-specific tip adhesin of Escherichia coli P-fimbriae is needed for pyelonephritis to occur in the normal urinary tract. Proc Natl Acad Sci USA 91:11889–11893.
202. Bock K, Breimer ME, Brignole A, Hansson GC, Karlsson K-A, Larson G, Leffler H, Samuelsson BE, Strömberg N, Edén CS, Thurin J. 1985. Specificity of binding of a strain of uropathogenic Escherichia coli to Gal alpha 1----4Gal-containing glycosphingolipids. J Biol Chem 260:8545–8551.
203. Strömberg N, Marklund BI, Lund B, Ilver D, Hamers A, Gaastra W, Karlsson KA, Normark S. 1990. Host-specificity of uropathogenic Escherichia coli depends on differences in binding specificity to Gal alpha 1-4Gal-containing isoreceptors. EMBO J 9:2001–2010.
204. Johnson JR, Russo TA, Brown JJ, Stapleton A. 1998. papG alleles of Escherichia coli strains causing first-episode or recurrent acute cystitis in adult women. J Infect Dis 177:97–101.
205. Roberts JA, Hardaway K, Kaack B, Fussell EN, Baskin G. 1984. Prevention of pyelonephritis by immunization with P-fimbriae. J Urol 131:602–607.
206. O’Hanley P, Lark D, Falkow S, Schoolnik G. 1985. Molecular basis of Escherichia coli colonization of the upper urinary tract in BALB/c mice. Gal-Gal pili immunization prevents Escherichia coli pyelonephritis in the BALB/c mouse model of human pyelonephritis. J Clin Invest 75:347–360.
207. Lane MC, Mobley HLT. 2007. Role of P-fimbrial-mediated adherence in pyelonephritis and persistence of uropathogenic Escherichia coli (UPEC) in the mammalian kidney. Kidney Int 72:19–25.
208. Hedlund M, Svensson M, Nilsson A, Duan RD, Svanborg C. 1996. Role of the ceramide-signaling pathway in cytokine responses to P-fimbriated Escherichia coli. J Exp Med 183:1037–1044.
209. Hedlund M, Wachtler C, Johansson E, Hang L, Somerville JE, Darveau RP, Svanborg C. 1999. P fimbriae-dependent, lipopolysaccharide-independent activation of epithelial cytokine responses. Mol Microbiol 33:693–703.
210. Bergsten G, Samuelsson M, Wullt B, Leijonhufvud I, Fischer H, Svanborg C. 2004. PapG-dependent adherence breaks mucosal inertia and triggers the innate host response. J Infect Dis 189:1734–1742.
211. Bergsten G, Wullt B, Svanborg C. 2005. Escherichia coli, fimbriae, bacterial persistence and host response induction in the human urinary tract. Int J Med Microbiol 295:487–502.
212. Fischer H, Ellström P, Ekström K, Gustafsson L, Gustafsson M, Svanborg C. 2007. Ceramide as a TLR4 agonist; a putative signalling intermediate between sphingolipid receptors for microbial ligands and TLR4. Cell Microbiol 9:1239–1251.
213. Rice JC, Peng T, Spence JS, Wang HQ, Goldblum RM, Corthésy B, Nowicki BJ. 2005. Pyelonephritic Escherichia coli expressing P fimbriae decrease immune response of the mouse kidney. J Am Soc Nephrol 16:3583–3591.
214. Zhang JP, Normark S. 1996. Induction of gene expression in Escherichia coli after pilus-mediated adherence. Science 273:1234–1236.
215. Bernier C, Gounon P, Le Bouguénec C. 2002. Identification of an aggregative adhesion fimbria (AAF) type III-encoding operon in enteroaggregative Escherichia coli as a sensitive probe for detecting the AAF-encoding operon family. Infect Immun 70:4302–4311.
216. Boisen N, Struve C, Scheutz F, Krogfelt KA, Nataro JP. 2008. New adhesin of enteroaggregative Escherichia coli related to the Afa/Dr/AAF family. Infect Immun 76:3281–3292.
217. Czeczulin JR, Balepur S, Hicks S, Phillips A, Hall R, Kothary MH, Navarro-Garcia F, Nataro JP. 1997. Aggregative adherence fimbria II, a second fimbrial antigen mediating aggregative adherence in enteroaggregative Escherichia coli. Infect Immun 65:4135–4145.
218. Nataro JP, Yikang D, Giron JA, Savarino SJ, Kothary MH, Hall R. 1993. Aggregative adherence fimbria I expression in enteroaggregative Escherichia coli requires two unlinked plasmid regions. Infect Immun 61:1126–1131.
219. Donnenberg M. 2013. Escherichia coli: Pathotypes and Principles of Pathogenesis. Academic Press, San Diego, CA.
220. Sheikh J, Czeczulin JR, Harrington S, Hicks S, Henderson IR, Le Bouguénec C, Gounon P, Phillips A, Nataro JP. 2002. A novel dispersin protein in enteroaggregative Escherichia coli. J Clin Invest 110:1329–1337.
221. Nataro JP, Deng Y, Maneval DR, German AL, Martin WC, Levine MM. 1992. Aggregative adherence fimbriae I of enteroaggregative Escherichia coli mediate adherence to HEp-2 cells and hemagglutination of human erythrocytes. Infect Immun 60:2297–2304.
222. Torres AG, Zhou X, Kaper JB. 2005. Adherence of diarrheagenic Escherichia coli strains to epithelial cells. Infect Immun 73:18–29.
223. Elias WP Jr, Czeczulin JR, Henderson IR, Trabulsi LR, Nataro JP. 1999. Organization of biogenesis genes for aggregative adherence fimbria II defines a virulence gene cluster in enteroaggregative Escherichia coli. J Bacteriol 181:1779–1785.
224. Farfan MJ, Inman KG, Nataro JP. 2008. The major pilin subunit of the AAF/II fimbriae from enteroaggregative Escherichia coli mediates binding to extracellular matrix proteins. Infect Immun 76:4378–4384.
225. Harrington SM, Dudley EG, Nataro JP. 2006. Pathogenesis of enteroaggregative Escherichia coli infection. FEMS Microbiol Lett 254:12–18.
226. Steiner TS, Lima AA, Nataro JP, Guerrant RL. 1998. Enteroaggregative Escherichia coli produce intestinal inflammation and growth impairment and cause interleukin-8 release from intestinal epithelial cells. J Infect Dis 177:88–96.
227. Väisänen-Rhen V. 1984. Fimbria-like hemagglutinin of Escherichia coli O75 strains. Infect Immun 46:401–407.
228. Nowicki B, Svanborg-Edén C, Hull R, Hull S. 1989. Molecular analysis and epidemiology of the Dr hemagglutinin of uropathogenic Escherichia coli. Infect Immun 57:446–451.
229. Nowicki B, Barrish JP, Korhonen T, Hull RA, Hull SI. 1987. Molecular cloning of the Escherichia coli O75X adhesin. Infect Immun 55:3168–3173.
230. Bilge SS, Apostol JM Jr, Fullner KJ, Moseley SL. 1993. Transcriptional organization of the F1845 fimbrial adhesin determinant of Escherichia coli. Mol Microbiol 7:993–1006.
231. Bilge SS, Clausen CR, Lau W, Moseley SL. 1989. Molecular characterization of a fimbrial adhesin, F1845, mediating diffuse adherence of diarrhea-associated Escherichia coli to HEp-2 cells. J Bacteriol 171:4281–4289.
232. Pham TQ, Goluszko P, Popov V, Nowicki S, Nowicki BJ. 1997. Molecular cloning and characterization of Dr-II, a nonfimbrial adhesin-I-like adhesin isolated from gestational pyelonephritis-associated Escherichia coli that binds to decay-accelerating factor. Infect Immun 65:4309–4318.
233. Nowicki B, Moulds J, Hull R, Hull S. 1988. A hemagglutinin of uropathogenic Escherichia coli recognizes the Dr blood group antigen. Infect Immun 56:1057–1060.
234. Westerlund B, Kuusela P, Risteli J, Risteli L, Vartio T, Rauvala H, Virkola R, Korhonen TK. 1989. The O75X adhesin of uropathogenic Escherichia coli is a type IV collagen-binding protein. Mol Microbiol 3:329–337.
235. Westerlund B, Korhonen TK. 1993. Bacterial proteins binding to the mammalian extracellular matrix. Mol Microbiol 9:687–694.
236. Fujita T, Inoue T, Ogawa K, Iida K, Tamura N. 1987. The mechanism of action of decay-accelerating factor (DAF). DAF inhibits the assembly of C3 convertases by dissociating C2a and Bb. J Exp Med 166:1221–1228.
237. Lublin DM, Atkinson JP. 1989. Decay-accelerating factor: biochemistry, molecular biology, and function. Annu Rev Immunol 7:35–58.
238. Berger CN, Billker O, Meyer TF, Servin AL, Kansau I. 2004. Differential recognition of members of the carcinoembryonic antigen family by Afa/Dr adhesins of diffusely adhering Escherichia coli (Afa/Dr DAEC). Mol Microbiol 52:963–983.
239. Muenzner P, Kengmo Tchoupa A, Klauser B, Brunner T, Putze J, Dobrindt U, Hauck CR. 2016. Uropathogenic E. coli exploit CEA to promote colonization of the urogenital tract mucosa. PLoS Pathog 12:e1005608. doi:10.1371/journal.ppat.1005608.
240. Kaul AK, Khan S, Martens MG, Crosson JT, Lupo VR, Kaul R. 1999. Experimental gestational pyelonephritis induces preterm births and low birth weights in C3H/HeJ mice. Infect Immun 67:5958–5966.
241. Goluszko P, Niesel D, Nowicki B, Selvarangan R, Nowicki S, Hart A, Pawelczyk E, Das M, Urvil P, Hasan R. 2001. Dr operon-associated invasiveness of Escherichia coli from pregnant patients with pyelonephritis. Infect Immun 69:4678–4680.
242. Hart A, Nowicki BJ, Reisner B, Pawelczyk E, Goluszko P, Urvil P, Anderson G, Nowicki S. 2001. Ampicillin-resistant Escherichia coli in gestational pyelonephritis: increased occurrence and association with the colonization factor Dr adhesin. J Infect Dis 183:1526–1529.
243. Bétis F, Brest P, Hofman V, Guignot J, Bernet-Camard MF, Rossi B, Servin A, Hofman P. 2003. The Afa/Dr adhesins of diffusely adhering Escherichia coli stimulate interleukin-8 secretion, activate mitogen-activated protein kinases, and promote polymorphonuclear transepithelial migration in T84 polarized epithelial cells. Infect Immun 71:1068–1074.
244. Bétis F, Brest P, Hofman V, Guignot J, Kansau I, Rossi B, Servin A, Hofman P. 2003. Afa/Dr diffusely adhering Escherichia coli infection in T84 cell monolayers induces increased neutrophil transepithelial migration, which in turn promotes cytokine-dependent upregulation of decay-accelerating factor (CD55), the receptor for Afa/Dr adhesins. Infect Immun 71:1774–1783.
245. Cane G, Moal VL, Pagès G, Servin AL, Hofman P, Vouret-Craviari V. 2007. Up-regulation of intestinal vascular endothelial growth factor by Afa/Dr diffusely adhering Escherichia coli. PLoS One 2:e1359. doi:10.1371/journal.pone.0001359.
246. Hacker J, Morschhauser J. 1994. S and F1C Fimbriae, p 27–36. In Klemm P (ed), Fimbriae: Adhesion, Genetics, Biogenesis, and Vaccines. CRC Press, Boca Raton.
247. Pere A, Leinonen M, Väisänen-Rhen V, Rhen M, Korhonen TK. 1985. Occurrence of type-1C fimbriae on Escherichia coli strains isolated from human extraintestinal infections. J Gen Microbiol 131:1705–1711.
248. Khan AS, Kniep B, Oelschlaeger TA, Van Die I, Korhonen T, Hacker J. 2000. Receptor structure for F1C fimbriae of uropathogenic Escherichia coli. Infect Immun 68:3541–3547.
249. van Die I, van Megen I, Hoekstra W, Bergmans H. 1984. Molecular organisation of the genes involved in the production of F7(2) fimbriae, causing mannose-resistant haemagglutination, of a uropathogenic Escherichia coli 06:K2:H1:F7 strain. Mol Gen Genet 194:528–533.
250. Virkola R, Westerlund B, Holthöfer H, Parkkinen J, Kekomäki M, Korhonen TK. 1988. Binding characteristics of Escherichia coli adhesins in human urinary bladder. Infect Immun 56:2615–2622.
251. Klemm P, Christiansen G, Kreft B, Marre R, Bergmans H. 1994. Reciprocal exchange of minor components of type 1 and F1C fimbriae results in hybrid organelles with changed receptor specificities. J Bacteriol 176:2227–2234.
252. Klemm P, Jørgensen BJ, Kreft B, Christiansen G. 1995. The export systems of type 1 and F1C fimbriae are interchangeable but work in parental pairs. J Bacteriol 177:621–627.
253. Kreft B, Carstensen O, Straube E, Bohnet S, Hacker J, Marre R. 1992. Adherence to and cytotoxicity of Escherichia coli for eucaryotic cell lines quantified by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide). Zentralbl Bakteriol 276:231–242.
254. Marre R, Kreft B, Hacker J. 1990. Genetically engineered S and F1C fimbriae differ in their contribution to adherence of Escherichia coli to cultured renal tubular cells. Infect Immun 58:3434–3437.
255. Lasaro MA, Salinger N, Zhang J, Wang Y, Zhong Z, Goulian M, Zhu J. 2009. F1C fimbriae play an important role in biofilm formation and intestinal colonization by the Escherichia coli commensal strain Nissle 1917. Appl Environ Microbiol 75:246–251.
256. Bäckhed F, Alsén B, Roche N, Angström J, von Euler A, Breimer ME, Westerlund-Wikström B, Teneberg S, Richter-Dahlfors A. 2002. Identification of target tissue glycosphingolipid receptors for uropathogenic, F1C-fimbriated Escherichia coli and its role in mucosal inflammation. J Biol Chem 277:18198–18205.
257. Korhonen TK, Valtonen MV, Parkkinen J, Väisänen-Rhen V, Finne J, Orskov F, Orskov I, Svenson SB, Mäkelä PH. 1985. Serotypes, hemolysin production, and receptor recognition of Escherichia coli strains associated with neonatal sepsis and meningitis. Infect Immun 48:486–491.
258. Hacker J. 1992. Role of fimbrial adhesins in the pathogenesis of Escherichia coli infections. Can J Microbiol 38:720–727.
259. Korhonen TK, Parkkinen J, Hacker J, Finne J, Pere A, Rhen M, Holthöfer H. 1986. Binding of Escherichia coli S fimbriae to human kidney epithelium. Infect Immun 54:322–327.
260. Hacker J, Schmidt G, Hughes C, Knapp S, Marget M, Goebel W. 1985. Cloning and characterization of genes involved in production of mannose-resistant, neuraminidase-susceptible (X) fimbriae from a uropathogenic O6:K15:H31 Escherichia coli strain. Infect Immun 47:434–440.
261. Schmoll T, Morschhäuser J, Ott M, Ludwig B, van Die I, Hacker J. 1990. Complete genetic organization and functional aspects of the Escherichia coli S fimbrial adhesion determinant: nucleotide sequence of the genes sfa B, C, D, E, F. Microb Pathog 9:331–343.
262. Morschhäuser J, Vetter V, Korhonen T, Uhlin BE, Hacker J. 1993. Regulation and binding properties of S fimbriae cloned from E. coli strains causing urinary tract infection and meningitis. Zentralbl Bakteriol 278:165–176.
263. Dobrindt U, Blum-Oehler G, Hartsch T, Gottschalk G, Ron EZ, Fünfstück R, Hacker J. 2001. S-Fimbria-encoding determinant sfa(I) is located on pathogenicity island III(536) of uropathogenic Escherichia coli strain 536. Infect Immun 69:4248–4256.
264. Knight SD, Choudhury D, Hultgren S, Pinkner J, Stojanoff V, Thompson A. 2002. Structure of the S pilus periplasmic chaperone SfaE at 2.2 A resolution. Acta Crystallogr D Biol Crystallogr 58:1016–1022.
265. Korhonen TK, Väisänen-Rhen V, Rhen M, Pere A, Parkkinen J, Finne J. 1984. Escherichia coli fimbriae recognizing sialyl galactosides. J Bacteriol 159:762–766.
266. Wang Y, Wen ZG, Kim KS. 2004. Role of S fimbriae in Escherichia coli K1 binding to brain microvascular endothelial cells in vitro and penetration into the central nervous system in vivo. Microb Pathog 37:287–293.
267. Sarén A, Virkola R, Hacker J, Korhonen TK. 1999. The cellular form of human fibronectin as an adhesion target for the S fimbriae of meningitis-associated Escherichia coli. Infect Immun 67:2671–2676.
268. Virkola R, Parkkinen J, Hacker J, Korhonen TK. 1993. Sialyloligosaccharide chains of laminin as an extracellular matrix target for S fimbriae of Escherichia coli. Infect Immun 61:4480–4484.
269. Parkkinen J, Hacker J, Korhonen TK. 1991. Enhancement of tissue plasminogen activator-catalyzed plasminogen activation by Escherichia coli S fimbriae associated with neonatal septicaemia and meningitis. Thromb Haemost 65:483–486.
270. Perez-Casal J, Swartley JS, Scott JR. 1990. Gene encoding the major subunit of CS1 pili of human enterotoxigenic Escherichia coli. Infect Immun 58:3594–3600.
271. Caron J, Coffield LM, Scott JR. 1989. A plasmid-encoded regulatory gene, rns, required for expression of the CS1 and CS2 adhesins of enterotoxigenic Escherichia coli. Proc Natl Acad Sci USA 86:963–967.
272. Murphree D, Froehlich B, Scott JR. 1997. Transcriptional control of genes encoding CS1 pili: negative regulation by a silencer and positive regulation by Rns. J Bacteriol 179:5736–5743.
273. Jordi BJ, Willshaw GA, van der Zeijst BA, Gaastra W. 1992. The complete nucleotide sequence of region 1 of the CFA/I fimbrial operon of human enterotoxigenic Escherichia coli. DNA Seq 2:257–263.
274. Smith HR, Willshaw GA, Rowe B. 1982. Mapping of a plasmid, coding for colonization, factor antigen I and heat-stable enterotoxin production, isolated from an enterotoxigenic strain of Escherichia coli. J Bacteriol 149:264–275.
275. Savelkoul PH, Willshaw GA, McConnell MM, Smith HR, Hamers AM, van der Zeijst BA, Gaastra W. 1990. Expression of CFA/I fimbriae is positively regulated. Microb Pathog 8:91–99.
276. Jordi BJ, Dagberg B, de Haan LA, Hamers AM, van der Zeijst BA, Gaastra W, Uhlin BE. 1992. The positive regulator CfaD overcomes the repression mediated by histone-like protein H-NS (H1) in the CFA/I fimbrial operon of Escherichia coli. EMBO J 11:2627–2632.
277. Gaastra W, Svennerholm AM. 1996. Colonization factors of human enterotoxigenic Escherichia coli (ETEC). Trends Microbiol 4:444–452.
278. Li YF, Poole S, Rasulova F, McVeigh AL, Savarino SJ, Xia D. 2007. A receptor-binding site as revealed by the crystal structure of CfaE, the colonization factor antigen I fimbrial adhesin of enterotoxigenic Escherichia coli. J Biol Chem 282:23970–23980.
279. Sakellaris H, Balding DP, Scott JR. 1996. Assembly proteins of CS1 pili of enterotoxigenic Escherichia coli. Mol Microbiol 21:529–541.
280. Poole ST, McVeigh AL, Anantha RP, Lee LH, Akay YM, Pontzer EA, Scott DA, Bullitt E, Savarino SJ. 2007. Donor strand complementation governs intersubunit interaction of fimbriae of the alternate chaperone pathway. Mol Microbiol 63:1372–1384.
281. Bühler T, Hoschützky H, Jann K. 1991. Analysis of colonization factor antigen I, an adhesin of enterotoxigenic Escherichia coli O78:H11: fimbrial morphology and location of the receptor-binding site. Infect Immun 59:3876–3882.
282. Jansson L, Tobias J, Lebens M, Svennerholm AM, Teneberg S. 2006. The major subunit, CfaB, of colonization factor antigen i from enterotoxigenic Escherichia coli is a glycosphingolipid binding protein. Infect Immun 74:3488–3497.
283. Marron MB, Smyth CJ. 1995. Molecular analysis of the cso operon of enterotoxigenic Escherichia coli reveals that CsoA is the adhesin of CS1 fimbriae and that the accessory genes are interchangeable with those of the cfa operon. Microbiology 141:2849–2859.
284. Sakellaris H, Penumalli VR, Scott JR. 1999. The level of expression of the minor pilin subunit, CooD, determines the number of CS1 pili assembled on the cell surface of Escherichia coli. J Bacteriol 181:1694–1697.
285. Levine MM, Kaper JB, Black RE, Clements ML. 1983. New knowledge on pathogenesis of bacterial enteric infections as applied to vaccine development. Microbiol Rev 47:510–550.
286. Nagy B, Fekete PZ. 1999. Enterotoxigenic Escherichia coli (ETEC) in farm animals. Vet Res 30:259–284.
287. Boedeker EC. 2005. Enteric infections. Curr Opin Gastroenterol 21:1–3.
288. Qadri F, Svennerholm AM, Faruque AS, Sack RB. 2005. Enterotoxigenic Escherichia coli in developing countries: epidemiology, microbiology, clinical features, treatment, and prevention. Clin Microbiol Rev 18:465–483.
289. Humphries AD, Raffatellu M, Winter S, Weening EH, Kingsley RA, Droleskey R, Zhang S, Figueiredo J, Khare S, Nunes J, Adams LG, Tsolis RM, Bäumler AJ. 2003. The use of flow cytometry to detect expression of subunits encoded by 11 Salmonella enterica serotype Typhimurium fimbrial operons. Mol Microbiol 48:1357–1376.
290. Bäumler AJ, Tsolis RM, Heffron F. 1996. The lpf fimbrial operon mediates adhesion of Salmonella typhimurium to murine Peyer’s patches. Proc Natl Acad Sci USA 93:279–283.
291. Tsolis RM, Townsend SM, Miao EA, Miller SI, Ficht TA, Adams LG, Bäumler AJ. 1999. Identification of a putative Salmonella enterica serotype typhimurium host range factor with homology to IpaH and YopM by signature-tagged mutagenesis. Infect Immun 67:6385–6393.
292. Weening EH, Barker JD, Laarakker MC, Humphries AD, Tsolis RM, Bäumler AJ. 2005. The Salmonella enterica serotype Typhimurium lpf, bcf, stb, stc, std, and sth fimbrial operons are required for intestinal persistence in mice. Infect Immun 73:3358–3366.
293. Bäumler AJ, Heffron F. 1995. Identification and sequence analysis of lpfABCDE, a putative fimbrial operon of Salmonella typhimurium. J Bacteriol 177:2087–2097.
294. Darwin KH, Miller VL. 1999. Molecular basis of the interaction of Salmonella with the intestinal mucosa. Clin Microbiol Rev 12:405–428.
295. Bäumler AJ, Tsolis RM, Heffron F. 1997. Fimbrial adhesins of Salmonella typhimurium. Role in bacterial interactions with epithelial cells. Adv Exp Med Biol 412:149–158.
296. Bäumler AJ, Tsolis RM, Valentine PJ, Ficht TA, Heffron F. 1997. Synergistic effect of mutations in invA and lpfC on the ability of Salmonella typhimurium to cause murine typhoid. Infect Immun 65:2254–2259.
297. Norris TL, Kingsley RA, Bümler AJ. 1998. Expression and transcriptional control of the Salmonella typhimurium Ipf fimbrial operon by phase variation. Mol Microbiol 29:311–320.
298. Friedrich MJ, Kinsey NE, Vila J, Kadner RJ. 1993. Nucleotide sequence of a 13.9 kb segment of the 90 kb virulence plasmid of Salmonella typhimurium: the presence of fimbrial biosynthetic genes. Mol Microbiol 8:543–558.
299. Bäumler AJ, Tsolis RM, Bowe FA, Kusters JG, Hoffmann S, Heffron F. 1996. The pef fimbrial operon of Salmonella typhimurium mediates adhesion to murine small intestine and is necessary for fluid accumulation in the infant mouse. Infect Immun 64:61–68.
300. Bäumler AJ, Tsolis RM, Heffron F. 1996. Contribution of fimbrial operons to attachment to and invasion of epithelial cell lines by Salmonella typhimurium. Infect Immun 64:1862–1865.
301. Bäumler AJ, Gilde AJ, Tsolis RM, van der Velden AW, Ahmer BM, Heffron F. 1997. Contribution of horizontal gene transfer and deletion events to development of distinctive patterns of fimbrial operons during evolution of Salmonella serotypes. J Bacteriol 179:317–322.
302. Rotger R, Casadesús J. 1999. The virulence plasmids of Salmonella. Int Microbiol 2:177–184.
303. Clouthier SC, Müller KH, Doran JL, Collinson SK, Kay WW. 1993. Characterization of three fimbrial genes, sefABC, of Salmonella enteritidis. J Bacteriol 175:2523–2533.
304. Clouthier SC, Collinson SK, Kay WW. 1994. Unique fimbriae-like structures encoded by sefD of the SEF14 fimbrial gene cluster of Salmonella enteritidis. Mol Microbiol 12:893–901.
305. Edwards RA, Schifferli DM, Maloy SR. 2000. A role for Salmonella fimbriae in intraperitoneal infections. Proc Natl Acad Sci USA 97:1258–1262.
306. Zeiner SA, Dwyer BE, Clegg S. 2012. FimA, FimF, and FimH are necessary for assembly of type 1 fimbriae on Salmonella enterica serovar Typhimurium. Infect Immun 80:3289–3296.
307. Boyd EF, Hartl DL. 1999. Analysis of the type 1 pilin gene cluster fim in Salmonella: its distinct evolutionary histories in the 5′ and 3′ regions. J Bacteriol 181:1301–1308.
308. Duguid JP, Campbell I. 1969. Antigens of the type-1 fimbriae of salmonellae and other enterobacteria. J Med Microbiol 2:535–553.
309. Lockman HA, Curtiss R III. 1992. Virulence of non-type 1-fimbriated and nonfimbriated nonflagellated Salmonella typhimurium mutants in murine typhoid fever. Infect Immun 60:491–496.
310. van der Velden AW, Bäumler AJ, Tsolis RM, Heffron F. 1998. Multiple fimbrial adhesins are required for full virulence of Salmonella typhimurium in mice. Infect Immun 66:2803–2808.
311. Dibb-Fuller MP, Allen-Vercoe E, Thorns CJ, Woodward MJ. 1999. Fimbriae- and flagella-mediated association with and invasion of cultured epithelial cells by Salmonella enteritidis. Microbiology 145:1023–1031.
312. Dibb-Fuller MP, Woodward MJ. 2000. Contribution of fimbriae and flagella of Salmonella enteritidis to colonization and invasion of chicks. Avian Pathol 29:295–304.
313. De Buck J, Van Immerseel F, Haesebrouck F, Ducatelle R. 2004. Effect of type 1 fimbriae of Salmonella enterica serotype Enteritidis on bacteraemia and reproductive tract infection in laying hens. Avian Pathol 33:314–320.
314. Kuźmińska-Bajor M, Grzymajło K, Ugorski M. 2015. Type 1 fimbriae are important factors limiting the dissemination and colonization of mice by Salmonella Enteritidis and contribute to the induction of intestinal inflammation during Salmonella invasion. Front Microbiol 6:276. doi:10.3389/fmicb.2015.00276.
315. Kline KA, Fälker S, Dahlberg S, Normark S, Henriques-Normark B. 2009. Bacterial adhesins in host-microbe interactions. Cell Host Microbe 5:580–592.
316. Cusumano CK, Hultgren SJ. 2009. Bacterial adhesion--a source of alternate antibiotic targets. IDrugs 12:699–705.
317. Steadman D, Lo A, Waksman G, Remaut H. 2014. Bacterial surface appendages as targets for novel antibacterial therapeutics. Future Microbiol 9:887–900.
318. Allen RC, Popat R, Diggle SP, Brown SP. 2014. Targeting virulence: can we make evolution-proof drugs? Nat Rev Microbiol 12:300–308.
319. Zambelloni R, Marquez R, Roe AJ. 2015. Development of antivirulence compounds: a biochemical review. Chem Biol Drug Des 85:43–55.
320. Cegelski L, Marshall GR, Eldridge GR, Hultgren SJ. 2008. The biology and future prospects of antivirulence therapies. Nat Rev Microbiol 6:17–27.
321. World Health Organization. 2014. Antimcribial Resistance: Global Report on Surveillance. WHO Press.
322. Centers for Disease Control and Prevention. 2013. Antibiotic Resistance Threats in the United States, 2013. https://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf
323. Fauci AS, Morens DM. 2012. The perpetual challenge of infectious diseases. N Engl J Med 366:454–461.
324. Spellberg B, Blaser M, Guidos RJ, Boucher HW, Bradley JS, Eisenstein BI, Gerding D, Lynfield R, Reller LB, Rex J, Schwartz D, Septimus E, Tenover FC, Gilbert DN, Infectious Diseases Society of America (IDSA). 2011. Combating antimicrobial resistance: policy recommendations to save lives. Clin Infect Dis 52(Suppl 5):S397–S428.
325. Thankavel K, Madison B, Ikeda T, Malaviya R, Shah AH, Arumugam PM, Abraham SN. 1997. Localization of a domain in the FimH adhesin of Escherichia coli type 1 fimbriae capable of receptor recognition and use of a domain-specific antibody to confer protection against experimental urinary tract infection. J Clin Invest 100:1123–1136.
326. Roberts JA, Kaack MB, Baskin G, Chapman MR, Hunstad DA, Pinkner JS, Hultgren SJ. 2004. Antibody responses and protection from pyelonephritis following vaccination with purified Escherichia coli PapDG protein. J Urol 171:1682–1685.
327. Poggio TV, La Torre JL, Scodeller EA. 2006. Intranasal immunization with a recombinant truncated FimH adhesin adjuvanted with CpG oligodeoxynucleotides protects mice against uropathogenic Escherichia coli challenge. Can J Microbiol 52:1093–1102.
328. Tchesnokova V, Aprikian P, Kisiela D, Gowey S, Korotkova N, Thomas W, Sokurenko E. 2011. Type 1 fimbrial adhesin FimH elicits an immune response that enhances cell adhesion of Escherichia coli. Infect Immun 79:3895–3904.
329. Cusumano CK, Pinkner JS, Han Z, Greene SE, Ford BA, Crowley JR, Henderson JP, Janetka JW, Hultgren SJ. 2011. Treatment and prevention of urinary tract infection with orally active FimH inhibitors. Sci Transl Med 3:109ra115. doi:10.1126/scitranslmed.3003021.
330. Klein T, Abgottspon D, Wittwer M, Rabbani S, Herold J, Jiang X, Kleeb S, Lüthi C, Scharenberg M, Bezençon J, Gubler E, Pang L, Smiesko M, Cutting B, Schwardt O, Ernst B. 2010. FimH antagonists for the oral treatment of urinary tract infections: from design and synthesis to in vitro and in vivo evaluation. J Med Chem 53:8627–8641.
331. Totsika M, Kostakioti M, Hannan TJ, Upton M, Beatson SA, Janetka JW, Hultgren SJ, Schembri MA. 2013. A FimH inhibitor prevents acute bladder infection and treats chronic cystitis caused by multidrug-resistant uropathogenic Escherichia coli ST131. J Infect Dis 208:921–928.
332. Guiton PS, Cusumano CK, Kline KA, Dodson KW, Han Z, Janetka JW, Henderson JP, Caparon MG, Hultgren SJ. 2012. Combinatorial small-molecule therapy prevents uropathogenic Escherichia coli catheter-associated urinary tract infections in mice. Antimicrob Agents Chemother 56:4738–4745.
333. Salminen A, Loimaranta V, Joosten JA, Khan AS, Hacker J, Pieters RJ, Finne J. 2007. Inhibition of P-fimbriated Escherichia coli adhesion by multivalent galabiose derivatives studied by a live-bacteria application of surface plasmon resonance. J Antimicrob Chemother 60:495–501.
334. Pinkner JS, Remaut H, Buelens F, Miller E, Aberg V, Pemberton N, Hedenström M, Larsson A, Seed P, Waksman G, Hultgren SJ, Almqvist F. 2006. Rationally designed small compounds inhibit pilus biogenesis in uropathogenic bacteria. Proc Natl Acad Sci USA 103:17897–17902.
335. Svensson A, Larsson A, Emtenäs H, Hedenström M, Fex T, Hultgren SJ, Pinkner JS, Almqvist F, Kihlberg J. 2001. Design and evaluation of pilicides: potential novel antibacterial agents directed against uropathogenic Escherichia coli. ChemBioChem 2:915–918.
336. Chorell E, Pinkner JS, Bengtsson C, Banchelin TS, Edvinsson S, Linusson A, Hultgren SJ, Almqvist F. 2012. Mapping pilicide anti-virulence effect in Escherichia coli, a comprehensive structure-activity study. Bioorg Med Chem 20:3128–3142.
337. Greene SE, Pinkner JS, Chorell E, Dodson KW, Shaffer CL, Conover MS, Livny J, Hadjifrangiskou M, Almqvist F, Hultgren SJ. 2014. Pilicide ec240 disrupts virulence circuits in uropathogenic Escherichia coli. MBio 5:e02038. doi:10.1128/mBio.02038-14.
338. Cegelski L, Pinkner JS, Hammer ND, Cusumano CK, Hung CS, Chorell E, Aberg V, Walker JN, Seed PC, Almqvist F, Chapman MR, Hultgren SJ. 2009. Small-molecule inhibitors target Escherichia coli amyloid biogenesis and biofilm formation. Nat Chem Biol 5:913–919.
339. Lo AW, Van de Water K, Gane PJ, Chan AW, Steadman D, Stevens K, Selwood DL, Waksman G, Remaut H. 2014. Suppression of type 1 pilus assembly in uropathogenic Escherichia coli by chemical inhibition of subunit polymerization. J Antimicrob Chemother 69:1017–1026.
340. Shamir ER, Warthan M, Brown SP, Nataro JP, Guerrant RL, Hoffman PS. 2010. Nitazoxanide inhibits biofilm production and hemagglutination by enteroaggregative Escherichia coli strains by blocking assembly of AafA fimbriae. Antimicrob Agents Chemother 54:1526–1533.
341. Chahales P, Hoffman PS, Thanassi DG. 2016. Nitazoxanide Inhibits Pilus Biogenesis by Interfering with Folding of the Usher Protein in the Outer Membrane. Antimicrob Agents Chemother 60:2028–2038.
342. Klinth JE, Pinkner JS, Hultgren SJ, Almqvist F, Uhlin BE, Axner O. 2012. Impairment of the biomechanical compliance of P pili: a novel means of inhibiting uropathogenic bacterial infections? Eur Biophys J 41:285–295.
343. Van Loy CP, Sokurenko EV, Moseley SL. 2002. The major structural subunits of Dr and F1845 fimbriae are adhesins. Infect Immun 70:1694–1702.
344. Savarino SJ, Fox P, Deng Y, Nataro JP. 1994. Identification and characterization of a gene cluster mediating enteroaggregative Escherichia coli aggregative adherence fimbria I biogenesis. J Bacteriol 176:4949–4957.
345. Garcia M-I, Labigne A, Le Bouguenec C. 1994. Nucleotide sequence of the afimbrial-adhesin-encoding afa-3 gene cluster and its translocation via flanking IS1 insertion sequences. J Bacteriol 176:7601–7613.
346. Lalioui L, Le Bouguénec C. 2001. afa-8 Gene cluster is carried by a pathogenicity island inserted into the tRNA(Phe) of human and bovine pathogenic Escherichia coli isolates. Infect Immun 69:937–948.
347. Cantey JR, Blake RK, Williford JR, Moseley SL. 1999. Characterization of the Escherichia coli AF/R1 pilus operon: novel genes necessary for transcriptional regulation and for pilus-mediated adherence. Infect Immun 67:2292–2298.
348. Buckles EL, Bahrani-Mougeot FK, Molina A, Lockatell CV, Johnson DE, Drachenberg CB, Burland V, Blattner FR, Donnenberg MS. 2004. Identification and characterization of a novel uropathogenic Escherichia coli-associated fimbrial gene cluster. Infect Immun 72:3890–3901.
349. Korea CG, Ghigo JM, Beloin C. 2011. The sweet connection: Solving the riddle of multiple sugar-binding fimbrial adhesins in Escherichia coli: Multiple E. coli fimbriae form a versatile arsenal of sugar-binding lectins potentially involved in surface-colonisation and tissue tropism. BioEssays 33:300–311.
350. Jalajakumari MB, Thomas CJ, Halter R, Manning PA. 1989. Genes for biosynthesis and assembly of CS3 pili of CFA/II enterotoxigenic Escherichia coli: novel regulation of pilus production by bypassing an amber codon. Mol Microbiol 3:1685–1695.
351. Duthy TG, Manning PA, Heuzenroeder MW. 2002. Identification and characterization of assembly proteins of CS5 pili from enterotoxigenic Escherichia coli. J Bacteriol 184:1065–1077.
352. Wolf MK, de Haan LA, Cassels FJ, Willshaw GA, Warren R, Boedeker EC, Gaastra W. 1997. The CS6 colonization factor of human enterotoxigenic Escherichia coli contains two heterologous major subunits. FEMS Microbiol Lett 148:35–42.
353. Del Canto F, Botkin DJ, Valenzuela P, Popov V, Ruiz-Perez F, Nataro JP, Levine MM, Stine OC, Pop M, Torres AG, Vidal R. 2012. Identification of coli surface antigen 23, a novel adhesin of enterotoxigenic Escherichia coli. Infect Immun 80:2791–2801.
354. Gaastra W, Sommerfelt H, van Dijk L, Kusters JG, Svennerholm A-M, Grewal HMS. 2002. Antigenic variation within the subunit protein of members of the colonization factor antigen I group of fimbrial proteins in human enterotoxigenic Escherichia coli. Int J Med Microbiol 292:43–50.
355. Honarvar S, Choi BK, Schifferli DM. 2003. Phase variation of the 987P-like CS18 fimbriae of human enterotoxigenic Escherichia coli is regulated by site-specific recombinases. Mol Microbiol 48:157–171.
356. Grewal HM, Valvatne H, Bhan MK, van Dijk L, Gaastra W, Sommerfelt H. 1997. A new putative fimbrial colonization factor, CS19, of human enterotoxigenic Escherichia coli. Infect Immun 65:507–513.
357. Valvatne H, Sommerfelt H, Gaastra W, Bhan MK, Grewal HM. 1996. Identification and characterization of CS20, a new putative colonization factor of enterotoxigenic Escherichia coli. Infect Immun 64:2635–2642.
358. Bertin Y, Girardeau J-P, Der Vartanian M, Martin C. 1993. The ClpE protein involved in biogenesis of the CS31A capsule-like antigen is a member of a periplasmic chaperone family in gram-negative bacteria. FEMS Microbiol Lett 108:59–67.
359. Keller R, Ordoñez JG, de Oliveira RR, Trabulsi LR, Baldwin TJ, Knutton S. 2002. Afa, a diffuse adherence fibrillar adhesin associated with enteropathogenic Escherichia coli. Infect Immun 70:2681–2689.
360. Rendón MA, Saldaña Z, Erdem AL, Monteiro-Neto V, Vázquez A, Kaper JB, Puente JL, Girón JA. 2007. Commensal and pathogenic Escherichia coli use a common pilus adherence factor for epithelial cell colonization. Proc Natl Acad Sci USA 104:10637–10642.
361. Riegman N, van Die I, Leunissen J, Hoekstra W, Bergmans H. 1988. Biogenesis of F71 and F72 fimbriae of uropathogenic Escherichia coli: influence of the FsoF and FstFG proteins and localization of the Fso/FstE protein. Mol Microbiol 2:73–80.
362. van Die I, Spierings G, van Megen I, Zuidweg E, Hoekstra W, Bergmans H. 1985. Cloning and genetic organization of the gene cluster encoding F71 fimbriae of a uropathogenic Escherichia coli and comparison with the F72 gene cluster. FEMS Microbiol Lett 28:329–334.
363. Riegman N, Hoschützky H, van Die I, Hoekstra W, Jann K, Bergmans H. 1990. Immunocytochemical analysis of P-fimbrial structure: localization of minor subunits and the influence of the minor subunit FsoE on the biogenesis of the adhesin. Mol Microbiol 4:1193–1198.
364. Ulett GC, Mabbett AN, Fung KC, Webb RI, Schembri MA. 2007. The role of F9 fimbriae of uropathogenic Escherichia coli in biofilm formation. Microbiology 153:2321–2331.
365. Conover MS, Ruer S, Taganna J, Kalas V, De Greve H, Pinkner JS, Dodson KW, Remaut H, Hultgren SJ. 2016. Inflammation-induced adhesin-receptor interaction provides a fitness advantage to uropathogenic E. coli during chronic infection. Cell Host Microbe 20:482–492.
366. Lintermans P, Pohl P, Deboeck F, Bertels A, Schlicker C, Vandekerckhove J, Van Damme J, Van Montagu M, De Greve H. 1988. Isolation and nucleotide sequence of the F17-A gene encoding the structural protein of the F17 fimbriae in bovine enterotoxigenic Escherichia coli. Infect Immun 56:1475–1484.
367. Imberechts H, et al. 1992. Characterization of F107 fimbriae of Escherichia coli 107/86, which causes edema disease in pigs, and nucleotide sequence of the F107 major fimbrial subunit gene, fedA. Infect Immun 60:1963–1971.
368. Fairbrother JM, Lallier R, Leblanc L, Jacques M, Larivière S. 1988. Production and purification of Escherichia coli fimbrial antigen F165. FEMS Microbiol Lett 56:247–252.
369. Bakker D, Vader CE, Roosendaal B, Mooi FR, Oudega B, de Graaf FK. 1991. Structure and function of periplasmic chaperone-like proteins involved in the biosynthesis of K88 and K99 fimbriae in enterotoxigenic Escherichia coli. Mol Microbiol 5:875–886.
370. Scaletsky ICA, Michalski J, Torres AG, Dulguer MV, Kaper JB. 2005. Identification and characterization of the locus for diffuse adherence, which encodes a novel afimbrial adhesin found in atypical enteropathogenic Escherichia coli. Infect Immun 73:4753–4765.
371. Ahrens R, Ott M, Ritter A, Hoschützky H, Bühler T, Lottspeich F, Boulnois GJ, Jann K, Hacker J. 1993. Genetic analysis of the gene cluster encoding nonfimbrial adhesin I from an Escherichia coli uropathogen. Infect Immun 61:2505–2512.
372. Oh KH, Kim DW, Jung SM, Cho SH. 2014. Molecular characterization of Enterotoxigenic Escherichia coli strains isolated from diarrheal patients in Korea during 2003–2011. PLoS One 9:e96896. doi:10.1371/journal.pone.0096896.
373. Klemm P, Roos V, Ulett GC, Svanborg C, Schembri MA. 2006. Molecular characterization of the Escherichia coli asymptomatic bacteriuria strain 83972: the taming of a pathogen. Infect Immun 74:781–785.
374. Adams LM, Simmons CP, Rezmann L, Strugnell RA, Robins-Browne RM. 1997. Identification and characterization of a K88- and CS31A-like operon of a rabbit enteropathogenic Escherichia coli strain which encodes fimbriae involved in the colonization of rabbit intestine. Infect Immun 65:5222–5230.
375. Lymberopoulos MH, Houle S, Daigle F, Léveillé S, Brée A, Moulin-Schouleur M, Johnson JR, Dozois CM. 2006. Characterization of Stg fimbriae from an avian pathogenic Escherichia coli O78:K80 strain and assessment of their contribution to colonization of the chicken respiratory tract. J Bacteriol 188:6449–6459.
376. Spurbeck RR, Stapleton AE, Johnson JR, Walk ST, Hooton TM, Mobley HL. 2011. Fimbrial profiles predict virulence of uropathogenic Escherichia coli strains: contribution of ygi and yad fimbriae. Infect Immun 79:4753–4763.
377. Schifferli DM, Beachey EH, Taylor RK. 1991. Genetic analysis of 987P adhesion and fimbriation of Escherichia coli: the fas genes link both phenotypes. J Bacteriol 173:1230–1240.
378. Dean EA. 1990. Comparison of receptors for 987P pili of enterotoxigenic Escherichia coli in the small intestines of neonatal and older pig. Infect Immun 58:4030–4035.
379. Yue M, Rankin SC, Blanchet RT, Nulton JD, Edwards RA, Schifferli DM. 2012. Diversification of the Salmonella fimbriae: a model of macro- and microevolution. PLoS One 7:e38596. doi:10.1371/journal.pone.0038596.
380. Silva CA, Blondel CJ, Quezada CP, Porwollik S, Andrews-Polymenis HL, Toro CS, Zaldívar M, Contreras I, McClelland M, Santiviago CA. 2012. Infection of mice by Salmonella enterica serovar Enteritidis involves additional genes that are absent in the genome of serovar Typhimurium. Infect Immun 80:839–849.
381. Thomson NR, Clayton DJ, Windhorst D, Vernikos G, Davidson S, Churcher C, Quail MA, Stevens M, Jones MA, Watson M, Barron A, Layton A, Pickard D, Kingsley RA, Bignell A, Clark L, Harris B, Ormond D, Abdellah Z, Brooks K, Cherevach I, Chillingworth T, Woodward J, Norberczak H, Lord A, Arrowsmith C, Jagels K, Moule S, Mungall K, Sanders M, Whitehead S, Chabalgoity JA, Maskell D, Humphrey T, Roberts M, Barrow PA, Dougan G, Parkhill J. 2008. Comparative genome analysis of Salmonella Enteritidis PT4 and Salmonella Gallinarum 287/91 provides insights into evolutionary and host adaptation pathways. Genome Res 18:1624–1637.
382. Carnell SC, Bowen A, Morgan E, Maskell DJ, Wallis TS, Stevens MP. 2007. Role in virulence and protective efficacy in pigs of Salmonella enterica serovar Typhimurium secreted components identified by signature-tagged mutagenesis. Microbiology 153:1940–1952.
383. Dufresne K, Daigle F. 2017. Salmonella Fimbriae: What is the Clue to Their Hairdo? Current Topics in Salmonella and Salmonellosis. InTech.
384. Seth-Smith HMB, Fookes MC, Okoro CK, Baker S, Harris SR, Scott P, Pickard D, Quail MA, Churcher C, Sanders M, Harmse J, Dougan G, Parkhill J, Thomson NR. 2012. Structure, diversity, and mobility of the Salmonella pathogenicity island 7 family of integrative and conjugative elements within Enterobacteriaceae. J Bacteriol 194:1494–1504.
385. Porwollik S, Wong RM, McClelland M. 2002. Evolutionary genomics of Salmonella: gene acquisitions revealed by microarray analysis. Proc Natl Acad Sci USA 99:8956–8961.
386. Thorns CJ, Turcotte C, Gemmell CG, Woodward MJ. 1996. Studies into the role of the SEF14 fimbrial antigen in the pathogenesis of Salmonella enteritidis. Microb Pathog 20:235–246.
387. De Masi L, Yue M, Hu C, Rakov AV, Rankin SC, Schifferli DM. 2017. Cooperation of adhesin alleles in Salmonella-host tropism. MSphere 2:e00066–e00017.
388. Berrocal L, Fuentes JA, Trombert AN, Jofré MR, Villagra NA, Valenzuela LM, Mora GC. 2015. stg fimbrial operon from S. Typhi STH2370 contributes to association and cell disruption of epithelial and macrophage-like cells. Biol Res 48:34. doi:10.1186/s40659-015-0024-9.
389. Ernst RK, Dombroski DM, Merrick JM. 1990. Anaerobiosis, type 1 fimbriae, and growth phase are factors that affect invasion of HEp-2 cells by Salmonella typhimurium. Infect Immun 58:2014–2016.

Citations loading...


Article metrics loading...



Gram-negative bacteria assemble a variety of surface structures, including the hair-like organelles known as pili or fimbriae. Pili typically function in adhesion and mediate interactions with various surfaces, with other bacteria, and with other types of cells such as host cells. The chaperone/usher (CU) pathway assembles a widespread class of adhesive and virulence-associated pili. Pilus biogenesis by the CU pathway requires a dedicated periplasmic chaperone and integral outer membrane protein termed the usher, which forms a multifunctional assembly and secretion platform. This review addresses the molecular and biochemical aspects of the CU pathway in detail, focusing on the type 1 and P pili expressed by uropathogenic as model systems. We provide an overview of representative CU pili expressed by and , and conclude with a discussion of potential approaches to develop antivirulence therapeutics that interfere with pilus assembly or function.

Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Comment has been disabled for this content
Submit comment
Comment moderation successfully completed


Image of Figure 1
Figure 1

Pilus subunits translocate from the cytoplasm to the periplasm as unfolded polypeptides via the Sec system. Subunit folding occurs upon interaction with the pilus chaperone (yellow) in the periplasm. Chaperone-subunit complexes then interact with the OM usher for exchange of chaperone-subunit for subunit-subunit interactions, ordered assembly of the pilus fiber, and secretion through the usher channel to the cell surface. The usher is depicted with its β-barrel channel domain in the OM and its plug, N, C1, and C2 domains labeled. The N domain forms the initial binding site for chaperone-subunit complexes, and the C domains provide a second binding site for the assembling pilus fiber. Chaperone-adhesin complexes have the highest affinity for the usher and initiate pilus assembly by binding to the usher N domain, with subsequent handoff to the usher C domains. Repeated rounds of chaperone-subunit targeting to the usher N domain and subunit-subunit interaction then lead to assembly and secretion of the pilus fiber in a top-down manner. Models of fully assembled type 1 (Fim), P (Pap), and Afa pilus fibers are shown.

Citation: Werneburg G, Thanassi D. 2018. Pili Assembled by the Chaperone/Usher Pathway in and , EcoSal Plus 2018; doi:10.1128/ecosalplus.ESP-0007-2017
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2
Figure 2

(A) Gene clusters, including upstream regulatory regions, are shown for P (), type 1 (), and Dr/Afa pili, with the functions of the genes indicated. (B) Regulatory region of the gene cluster, shown in phase-OFF and phase-ON states. Lrp binding to the GATC site turns off expression from the promoter. Binding of Lrp, together with PapI, to the GATC site allows Dam methylation of GATC, resulting in phase-ON expression. Production of PapB during phase-ON expression initiates a positive feedback loop through upregulation of PapI. (C) Regulatory region of the gene cluster, showing the phase-OFF and phase-ON orientations of the switch region. The left and right inverted repeat sequences ( and ) that flank the S switch are indicated. Binding of H-NS maintains in the phase-OFF position, whereas binding of IHF and Lrp favors phase-ON expression.

Citation: Werneburg G, Thanassi D. 2018. Pili Assembled by the Chaperone/Usher Pathway in and , EcoSal Plus 2018; doi:10.1128/ecosalplus.ESP-0007-2017
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3
Figure 3

(A) Structure of a FimC-H chaperone-adhesin complex (PDB ID: 1QUN) from the type 1 pilus system. The FimC chaperone is in yellow and the FimH adhesin in green, with the FimH lectin and pilin domains indicated. The chaperone is engaged in donor strand complementation (DSC) with the subunit. The chaperone donates its G1 β-strand (in blue) to complete the Ig fold of the FimH pilin domain. (B) Structure of a FimG-FimH subunit-subunit complex (PDB ID: 4J3O) from the type 1 pilus system. FimH is depicted as in (A) and FimG is in orange. The N-terminal extension (Nte) of FimG is engaged in donor strand exchange (DSE) with FimH. The Nte of FimG completes the Ig fold of the FimH pilin domain. (C) Topology diagrams depicting the Ig folds of the FimG (orange) and FimF (red) pilin domains. FimF is depicted in DSC with the donated G1-strand of the FimC chaperone, which is inserted parallel to the FimF F-strand. FimG is depicted in DSE with the Nte of FimF, which is inserted antiparallel to the FimG F-strand. (D) and (E) Structures of the lectin domains of the FimH (type 1 pili; PDB ID: 1KLF) and PapG (P pili; PDB ID: 1J8R) adhesins, with bound mannose and globoside molecules, respectively. The sugars are depicted in dark gray stick representation.

Citation: Werneburg G, Thanassi D. 2018. Pili Assembled by the Chaperone/Usher Pathway in and , EcoSal Plus 2018; doi:10.1128/ecosalplus.ESP-0007-2017
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 4
Figure 4

(A) and (C) Structure of FimD (PDB ID: 3OHN), shown from side (A) and top (C) views. The transmembrane β-barrel channel domain is pictured in light blue and the plug domain in pink. The plug domain is positioned laterally within the β-barrel domain, closing the usher channel. The N, C1, and C2 domains are not present in this structure. (B and D) Structure of activated FimD (PDB ID: 3RFZ), shown from side (B) and top (D) views. The channel and plug domains are depicted as in (A), the N domain is in dark blue, the C1 domain is in cyan, and the C2 domain is in purple. In the activated usher, the plug is expelled from the channel and resides adjacent to the N domain in the periplasm.

Citation: Werneburg G, Thanassi D. 2018. Pili Assembled by the Chaperone/Usher Pathway in and , EcoSal Plus 2018; doi:10.1128/ecosalplus.ESP-0007-2017
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 5
Figure 5

(A) Cartoon depictions of domain organization and color coding for the Fim proteins shown in panels (B through F). (B) Structure of FimD (PDB ID: 3OHN) with the transmembrane β-barrel channel closed by the plug domain. (C) Structure of the FimD N domain bound to a FimC-FimH pilin domain complex (PDB ID: 1ZE3). (D) Structure of the activated FimD usher with bound FimC-H chaperone-adhesin complex (PDB ID: 3RFZ). The FimH lectin domain is inserted inside the usher channel and the FimH pilin domain and bound FimC chaperone are located at the usher C domains. The FimD plug domain resides adjacent to the N domain in the periplasm. Structure of the FimD-C-F-G-H type 1 pilus assembly intermediate (PDB ID: 4J3O). The FimF-G-H pilus tip fiber is traversing the usher channel, with FimH exposed to the cell surface, and FimF bound by FimC located at the usher C domains. (F) Model for type 1 pilus assembly at the FimD usher. In its resting () state, the FimD plug domain resides laterally within the usher channel (structure shown in B). The plug closes the usher channel and also functions to mask the C domains. Pilus assembly initiates with the binding of a FimC-H chaperone-adhesin complexes to the FimD N domain (step 1; structure shown in C). FimC-H binding to the N domain activates the usher by triggering opening of the plug domain and unmasking of the C domains. FimC-H then undergoes handoff from the N to the C domains, concomitant with insertion of the FimH lectin domain into the usher channel (step 2; structure shown in D). The usher N domain functions to recruit the next chaperone-subunit complex, FimC-G, from the periplasm (step 3). The FimC-G complex bound at usher N domain is perfectly positioned to undergo DSE with FimC-H bound at the C domains, forming the first link in the pilus fiber and displacing FimC from FimH. FimC-G is then handed off from the N to the C domains, concomitant with movement of the nascent pilus fiber through the usher channel toward the cell surface (step 4). Repeated cycles of chaperone-subunit recruitment and DSE (step 5) then result in assembly and secretion of the pilus tip (structure shown in E) and finally the pilus rod.

Citation: Werneburg G, Thanassi D. 2018. Pili Assembled by the Chaperone/Usher Pathway in and , EcoSal Plus 2018; doi:10.1128/ecosalplus.ESP-0007-2017
Permissions and Reprints Request Permissions
Download as Powerpoint


Generic image for table
Table 1

CU pili present in and

Citation: Werneburg G, Thanassi D. 2018. Pili Assembled by the Chaperone/Usher Pathway in and , EcoSal Plus 2018; doi:10.1128/ecosalplus.ESP-0007-2017

Supplemental Material

No supplementary material available for this content.

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