Pilicide ec240 disrupts virulence circuits in uropathogenic Escherichia coli

mBio

Volumn 5, Issue 6, 2014, Pages

  Greene, Sarah E ^a   Pinkner, Jerome S ^a   Chorell, Erik ^a,b   Dodson, Karen W ^a   Shaffer, Carrie L ^c   Conover, Matt S ^a   Livny, Jonathan ^d   Hadjifrangiskou, Maria ^c   Almqvist, Fredrik ^b   Hultgren, Scott J ^a  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UMEÅ UNIVERSITY   (Sweden)

^c VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d BROAD INSTITUTE OF MIT AND HARVARD   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIINFECTIVE AGENT; CHAPERONE; PAPB PROTEIN; PAPX PROTEIN; PILICIDE EC240; PROTEIN; SFAB PROTEIN; SFAX PROTEIN; UNCLASSIFIED DRUG; VIRULENCE FACTOR; ESCHERICHIA COLI PROTEIN;

ARTICLE; BACTERIAL GROWTH; BACTERIAL STRAIN; BACTERIAL VIRULENCE; BACTERIUM PILUS; BIOGENESIS; CONTROLLED STUDY; CYSTITIS; DOWN REGULATION; DRUG MECHANISM; FLAGELLUM; GENETIC TRANSCRIPTION; GRAM NEGATIVE BACTERIUM; GRAM NEGATIVE INFECTION; NONHUMAN; OPERON; PATHOGENESIS; PROTEIN EXPRESSION; PROTEOMICS; TRANSCRIPTOMICS; URINARY TRACT INFECTION; UROPATHOGENIC ESCHERICHIA COLI; DRUG EFFECTS; FIMBRIA; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GROWTH, DEVELOPMENT AND AGING; LOCOMOTION; METABOLISM; PHYSIOLOGY; VIRULENCE;

BACTERIA (MICROORGANISMS); ESCHERICHIA COLI; NEGIBACTERIA;

ANTI-BACTERIAL AGENTS; ESCHERICHIA COLI PROTEINS; FIMBRIAE, BACTERIAL; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, BACTERIAL; LOCOMOTION; UROPATHOGENIC ESCHERICHIA COLI; VIRULENCE; VIRULENCE FACTORS;

EID: 84920895336     PISSN: 21612129     EISSN: 21507511     Source Type: Journal    
DOI: 10.1128/mBio.02038-14     Document Type: Article

References (70)

1. Spellberg B, Guidos R, Gilbert D, Bradley J, Boucher HW, Scheld WM, Bartlett JG, Edwards J Jr, Infectious Diseases Society of America. 2008. The epidemic of antibiotic-resistant infections: a call to action for the medical community from the Infectious Diseases Society of America. Clin. Infect. Dis. 46:155–164. http://dx.doi.org/10.1086/524891.
2. Boucher HW, Talbot GH, Bradley JS, Edwards JE, Gilbert D, Rice LB, Scheld M, Spellberg B, Bartlett J. 2009. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin. Infect. Dis. 48:1–12. http://dx.doi.org/10.1086/591855.
3. 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. 3:109-115. http://dx.doi.org/10.1126/scitranslmed.3003021.
4. Sauer FG, Remaut H, Hultgren SJ, Waksman G. 2004. Fiber assembly by the chaperone-usher pathway. Biochim. Biophys. Acta 1694:259–267. http://dx.doi.org/10.1016/j.bbamcr.2004.02.010.
5. Holmgren A, Bränden CI. 1989. Crystal structure of chaperone protein PapD reveals an immunoglobulin fold. Nature 342:248–251. http://dx.doi.org/10.1038/342248a0.
6. 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. http://dx.doi.org/10.1126/science.285.5430.1058.
7. Barnhart MM, Sauer FG, Pinkner JS, Hultgren SJ. 2003. Chaperonesubunit- usher interactions required for donor strand exchange during bacterial pilus assembly. J. Bacteriol. 185:2723–2730. http://dx.doi.org/10.1128/JB.185.9.2723-2730.2003.
8. Wurpel DJ, Beatson SA, Totsika M, Petty NK, Schembri MA. 2012. Chaperone-usher fimbriae of Escherichia coli. PLoS One 8(1):e52835. http://dx.doi.org/10.1371/journal.pone.0052835.
9. Connell I, Agace W, Klemm P, Schembri M, Mârild S, Svanborg C. 1996. Type 1 fimbrial expression enhances Escherichia coli virulence for the urinary tract. Proc. Natl. Acad. Sci. U. S. A. 93:9827–9832. http://dx.doi.org/10.1073/pnas.93.18.9827.
10. Marre R, Hacker J, Henkel W, Goebel W. 1986. Contribution of cloned virulence factors from uropathogenic Escherichia coli strains to nephropathogenicity in an experimental rat pyelonephritis model. Infect. Immun. 54:761–767.
11. Hagberg L, Hull R, Hull S, Falkow S, Freter R, Svanborg Edén C. 1983. Contribution of adhesion to bacterial persistence in the mouse urinary tract. Infect. Immun. 40:265–272.
12. 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. http://dx.doi.org/10.1093/emboj/19.12.2803.
13. 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. http://dx.doi.org/10.1126/science.282.5393.1494.
14. Anderson GG, Dodson KW, Hooton TM, Hultgren SJ. 2004. Intracellular bacterial communities of uropathogenic Escherichia coli in urinary tract pathogenesis. Trends Microbiol. 12:424–430. http://dx.doi.org/10.1016/j.tim.2004.07.005.
15. 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. http://dx.doi.org/10.1111/j.1462-5822.2007.00952.x.
16. Song J, Bishop BL, Li G, Grady R, Stapleton A, Abraham SN. 2009. TLR4-mediated expulsion of bacteria from infected bladder epithelial cells. Proc. Natl. Acad. Sci. U. S. A. 106:14966–14971. http://dx.doi.org/10.1073/pnas.0900527106.
17. Rosen DA, Hooton TM, Stamm WE, Humphrey PA, Hultgren SJ. 2007. Detection of intracellular bacterial communities in human urinary tract infection. PLOS Med. 4:e329. http://dx.doi.org/10.1371/journal.pmed.0040329.
18. Nowicki B, Rhen M, Väisänen-Rhen V, Pere A, Korhonen TK. 1984. Immunofluorescence study of fimbrial phase variation in Escherichia coli KS71. J. Bacteriol. 160:691–695.
19. van der Woude MW, Bäumler AJ. 2004. Phase and antigenic variation in bacteria. Clin. Microbiol. Rev. 17:581–611. http://dx.doi.org/10.1128/CMR.17.3.581-611.2004.
20. Abraham JM, Freitag CS, Clements JR, Eisenstein BI. 1985. An invertible element of DNA controls phase variation of type 1 fimbriae of Escherichia coli. Proc. Natl. Acad. Sci. U. S. A. 82:5724–5727. http://dx.doi.org/10.1073/pnas.82.17.5724.
21. 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. http://dx.doi.org/10.1046/j.1365-2958.1996.311388.x.
22. Hannan TJ, Mysorekar IU, Chen SL, Walker JN, Jones JM, Pinkner JS, Hultgren SJ, Seed PC. 2008. LeuX tRNA-dependent and -independent mechanisms of Escherichia coli pathogenesis in acute cystitis. Mol. Microbiol. 67:116–128. http://dx.doi.org/10.1111/j.1365-2958.2007.06025.x.
23. Eisenstein BI, Sweet DS, Vaughn V, Friedman DI. 1987. Integration host factor is required for the DNA inversion that controls phase variation in Escherichia coli. Proc. Natl. Acad. Sci. U. S. A. 84:6506–6510. http://dx.doi.org/10.1073/pnas.84.18.6506.
24. Holden NJ, Gally DL. 2004. Switches, cross-talk and memory in Escherichia coli adherence. J. Med. Microbiol. 53:585–593. http://dx.doi.org/10.1099/jmm.0.05491-0.
25. Van der Woude MW, Low DA. 1994. Leucine-responsive regulatory protein and deoxyadenosine methylase control the phase variation and expression of the sfa and daa pili operons in Escherichia coli. Mol. Microbiol. 11:605–618. http://dx.doi.org/10.1111/j.1365-2958.1994.tb00340.x.
26. Müller CM, Aberg A, Straseviçiene J, Emody L, Uhlin BE, Balsalobre C. 2009. Type 1 fimbriae, a colonization factor of uropathogenic Escherichia coli, are controlled by the metabolic sensor CRP-cAMP. PLoS Pathog. 5(2):e1000303. http://dx.doi.org/10.1371/journal.ppat.1000303.
27. 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. http://dx.doi.org/10.1111/j.1365-2958.2009.06919.x.
28. 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. http://dx.doi.org/10.1046/j.1365-2958.2001.02656.x.
29. 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. http://dx.doi.org/10.1093/emboj/19.7.1450.
30. Sjöström AE, Balsalobre C, Emödy L, Westerlund-Wikström B, Hacker J, Uhlin BE. 2009. TheSfaXII protein from newborn meningitis E. coli is involved in regulation of motility and type 1 fimbriae expression. Microb. Pathog. 46:243–252. http://dx.doi.org/10.1016/j.micpath.2009.01.007.
31. Lane MC, Simms AN, Mobley HL. 2007. Complex interplay between type 1 fimbrial expression and flagellum-mediated motility of uropathogenic Escherichia coli. J. Bacteriol. 189:5523–5533. http://dx.doi.org/10.1128/JB.00434-07.
32. 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. http://dx.doi.org/10.1128/IAI.73.11.7588-7596.2005.
33. Simms AN, Mobley HL. 2008. PapX, a P fimbrial operon-encoded inhibitor of motility in uropathogenic Escherichia coli. Infect. Immun. 76: 4833–4841. http://dx.doi.org/10.1128/IAI.00630-08.
34. 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. http://dx.doi.org/10.1002/1439-7633(20011203)2:12_915::AID-CBIC915_3.3.CO;2-D.
35. Cegelski L, Pinkner JS, Hammer ND, Cusumano CK, Hung CS, Chorell E, Åberg 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(12):1–7. http://dx.doi.org/10.1038/nchembio0109-1.
36. 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. U. S. A. 103:17897–17902. http://dx.doi.org/10.1073/pnas.0606795103.
37. Chorell E, Pinkner JS, Phan G, Edvinsson S, Buelens F, Remaut H, Waksman G, Hultgren SJ, Almqvist F. 2010. Design and synthesis of C-2 substituted thiazolo and dihydrothiazolo ring-fused 2-pyridones: pilicides with increased antivirulence activity. J. Med. Chem. 53:5690–5695. http://dx.doi.org/10.1021/jm100470t.
38. Chorell E, Das P, Almqvist F. 2007. Diverse functionalization of thiazolo ring-fused 2-pyridones. J. Org. Chem. 72:4917–4924. http://dx.doi.org/10.1021/jo0704053.
39. 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. 2 0:3128–3142. http://dxdoiorg/101016/j.bmc.2012.01.048.
40. Dang HT, Chorell E, Uvell H, Pinkner JS, Hultgren SJ, Almqvist F. 2014. Syntheses and biological evaluation of 2-amino-3-acyltetrahydrobenzothiophene derivatives; antibacterial agents with antivirulence activity. Org. Biomol. Chem. 12:1942–1956. http://dx.doi.org/10.1039/c3ob42478b.
41. Aberg V, Hedenström M, Pinkner JS, Hultgren SJ, Almqvist F. 2005. C-terminal properties are important for ring-fused 2-pyridones that interfere with the chaperone function in uropathogenic E. coli. Org. Biomol. Chem. 3:3886–3892. http://dx.doi.org/10.1039/b509376g.
42. Aberg V, Fällman E, Axner O, Uhlin BE, Hultgren SJ, Almqvist F. 2007. Pilicides regulate pili expression in E. coli without affecting the functional properties of the pilus rod. Mol. Biosyst. 3:214–218. http://dx.doi.org/10.1039/b613441f.
43. Chen SL, Hung CS, Xu J, Reigstad CS, Magrini V, Sabo A, Blasiar D, Bieri T, Meyer RR, Ozersky P, Armstrong JR, Fulton RS, Latreille JP, Spieth J, Hooton TM, Mardis ER, Hultgren SJ, Gordon JI. 2006. Identification of genes subject to positive selection in uropathogenic strains of Escherichia coli: a comparative genomics approach. Proc. Natl. Acad. Sci. U. S. A. 103:5977–5982. http://dx.doi.org/10.1073/pnas.0600938103.
44. 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.
45. Jacob-Dubuisson F, Striker R, Hultgren SJ. 1994. Chaperone-assisted self-assembly of pili independent of cellular energy. J. Biol. Chem. 269: 12447–12455.
46. 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. U. S. A. 106:22439–22444. http://dx.doi.org/10.1073/pnas.0902179106.
47. Jones CH, Pinkner JS, Nicholes AV, Slonim LN, Abraham SN, Hultgren SJ. 1993. FimC is a periplasmic PapD-like chaperone that directs assembly of type 1 pili in bacteria. Proc. Natl. Acad. Sci. U. S. A. 90:8397–8401. http://dx.doi.org/10.1073/pnas.90.18.8397.
48. Kostakioti M, Hadjifrangiskou M, Cusumano CK, Hannan TJ, Janetka JW, Hultgren SJ. 2012. Distinguishing the contribution of type 1 pili from that of other QseB-misregulated factors when QseC is absent during urinary tract infection. Infect. Immun. 80:2826–2834. http://dx.doi.org/10.1128/IAI.00283-12.
49. Lane MC, Alteri CJ, Smith SN, Mobley HL. 2007. Expression of flagella is coincident with uropathogenic Escherichia coli ascension to the upper urinary tract. Proc. Natl. Acad. Sci. U. S. A. 104:16669–16674. http://dx.doi.org/10.1073/pnas.0607898104.
50. Wright KJ, Seed PC, Hultgren SJ. 2005. UropathogenicEscherichia coli flagella aid in efficient urinary tract colonization. Infect. Immun. 73: 7657–7668. http://dx.doi.org/10.1128/IAI.73.11.7657-7668.2005.
51. Terashima H, Kojima S, Homma M. 2008. Flagellar motility in bacteria structure and function of flagellar motor. Int. Rev. Cell Mol. Biol. 270: 39–85. http://dx.doi.org/10.1016/S1937-6448(08)01402-0.
52. Parkkinen J, Korhonen TK, Pere A, Hacker J, Soinila S. 1988. Binding sites in the rat brain for Escherichia coli S fimbriae associated with neonatal meningitis. J. Clin. Invest. 81:860 – 865. http://dx.doi.org/10.1172/JCI113395.
53. McClain MS, Blomfield IC, Eberhardt KJ, Eisenstein BI. 1993. Inversion-independent phase variation of type 1 fimbriae in Escherichia coli. J. Bacteriol. 175:4335–4344.
54. Dorman CJ, Higgins CF. 1987. Fimbrial phase variation in Escherichiacoli: dependence on integration host factor and homologies with other site-specific recombinases. J. Bacteriol. 169:3840–3843.
55. Reigstad CS, Hultgren SJ, Gordon JI. 2007. Functional genomic studies of uropathogenic Escherichia coli and host urothelial cells when intracellular bacterial communities are assembled. J. Biol. Chem. 282: 21259–21267. http://dx.doi.org/10.1074/jbc.M611502200.
56. 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. http://dx.doi.org/10.1126/science.276.5312.607.
57. 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. http://dx.doi.org/10.1097/01.ju.0000116123.05160.43.
58. Datsenko KA, Wanner BL. 2000. One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc. Natl. Acad. Sci. U. S. A. 97:6640–6645. http://dx.doi.org/10.1073/pnas.120163297.
59. O’Hanley P, Lark D, Normark S, Falkow S, Schoolnik GK. 1983. Mannose-sensitive and Gal-Gal binding Escherichia coli pili from recombinant strains. Chemical, functional, and serological properties. J. Exp. Med. 158:1713–1719. http://dx.doi.org/10.1084/jem.158.5.1713.
60. Schmoll T, Ott M, Oudega B, Hacker J. 1990. Use of a wild-type gene fusion to determine the influence of environmental conditions on expression of the S fimbrial adhesin in an Escherichia coli pathogen. J. Bacteriol. 172:5103–5111.
61. Pfaffl MW. 2001. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 29:e45. http://dx.doi.org/10.1093/nar/29.9.e45.
62. Gardner PP, Daub J, Tate JG, Nawrocki EP, Kolbe DL, Lindgreen S, Wilkinson AC, Finn RD, Griffiths-Jones S, Eddy SR, Bateman A. 2009. Rfam: updates to the RNA families database. Nucleic Acids Res. 37(Database issue):D136–D140. http://dx.doi.org/10.1093/nar/gkn766.
63. Li H, Durbin R. 1988. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25:1754–1760. http://dx.doi.org/10.1093/bioinformatics/btp324.
64. Mandlik A, Livny J, Robins WP, Ritchie JM, Mekalanos JJ, Waldor MK. 2011. RNA-Seq-based monitoring of infection-linked changes in Vibrio cholerae gene expression. Cell Host Microbe 10:165–174. http://dx.doi.org/10.1016/j.chom.2011.07.007.
65. Anders S, Huber W. 2010. Differential expression analysis for sequence count data. Genome Biol. 11:R106. http://dx.doi.org/10.1186/gb-2010-11-10-r106.
66. Hultgren SJ, Schwan WR, Schaeffer AJ, Duncan JL. 1986. Regulation of production of type 1 pili among urinary tract isolates of Escherichia coli. Infect. Immun. 54:613–620.
67. Rappsilber J, Ishihama Y, Mann M. 2003. Stop and go extraction tips for matrix-assisted laser desorption/ionization, nanoelectrospray, and LC/MS sample pretreatment in proteomics. Anal. Chem. 75:663–670. http://dx.doi.org/10.1021/ac026117i.
68. Thissen D, Steinberg L, Kuang D. 2002. Quick and easy implementation of the Benjamini-Hochberg procedure for controlling the false positive rate in multiple comparisons. J. Educ. Behav. Statist. 27:77–83. http://dx.doi.org/10.3102/10769986027001077.
69. Amann E, Ochs B, Abel KJ. 1988. Tightly regulated tac promoter vectors useful for the expression of unfused and fused proteins in Escherichia coli. Gene 69:301–315. http://dx.doi.org/10.1016/0378-1119(88)90440-4.
70. O’Toole GA, Kolter R. 1998. Initiation of biofilm formation in Pseudomonas fluorescens WCS365 proceeds via multiple, convergent signalling pathways: a genetic analysis. Mol. Microbiol. 28:449–461. http://dx.doi.org/10.1046/j.1365-2958.1998.00797.x.