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The Role of the Outer Membrane of Gram-negative Bacteria in Antibiotic Resistance: Ajax’ Shield or Achilles’ Heel?

Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 211)

Abstract

There has been an enormous increase in our knowledge of the fundamental steps in the biosynthesis and assembly of the outer membrane of Gram-negative bacteria. Lipopolysaccharide is a major component of the outer membrane of Gram-negative bacteria as is peptidoglycan. Porins, efflux pumps and other transport proteins of the outer membrane are also present. It is clear that there are numerous essential proteins that have the potential to be targets for novel antimicrobial agents. Progress, however, has been slow. Much of the emphasis has been on cytoplasmic processes that were better understood earlier on, but have the drawback that two penetration barriers, with different permeability properties, have to be crossed. With the increased understanding of the late-stage events occurring in the periplasm, it may be possible to shift focus to these more accessible targets. Nevertheless, getting drugs across the outer membrane will remain a challenge to the ingenuity of the medicinal chemist.

Keywords

Gram-negative bacteria Outer membrane Lipopolysaccharide Lipid A Peptidoglycan Transglycosylase Transpeptidase Protein secretion 

References

  1. Baasov T, Belakov V (1999) Recent Res Develop Org Chem 3:195–206Google Scholar
  2. Baasov T, Belakov V (2000) Drug Develop Res 50:416–424Google Scholar
  3. Baasov V, Tkacz T, Sheffer-Dee-Noor S, Belakhov V (2001) Curr Org Chem 5:127–138Google Scholar
  4. Baizman ER, Branstrom AA, Longley CB, Allanson N, Sofia MJ, Gange D, Goldman RC (2000) Microbiology 146:3129–3140PubMedGoogle Scholar
  5. Banemann A, Deppisch H, Gross R (1998) Infect Immun 66:5607–5612PubMedGoogle Scholar
  6. Banerjee DK (1989) J Biol Chem 264:2024–2028PubMedGoogle Scholar
  7. Bastin DA, Brown PK, Haase A, Stevenson G, Reeves PR (1993) Mol Microbiol 7:725–734PubMedGoogle Scholar
  8. Batchelor RA, Alifiano P, Biffali E, Hull SI, Hull RA (1992) J Bacteriol 174:5228–5236PubMedGoogle Scholar
  9. Baum EZ, Crespo-Carbone SM, Klinger A, Foleno BD, Turchi I, Macielag M, Bush K (2007) Antimicrob Agents Chemother 51:4420–4426PubMedGoogle Scholar
  10. Baum EZ, Crespo-Carbone SM, Foleno BD, Simon LD, Guillemont J, Macielag M, Bush K (2009) Antimicrob Agents Chemother 53:3240–3247PubMedGoogle Scholar
  11. Benson RE, Gottlin EB, Christensen DJ, Hamilton PT (2003) Antimicrob Agents Chemother 47:2875–2881PubMedGoogle Scholar
  12. Bigham EC, Gragg CE, Hall WR, Kelsey JE, Mallory WR, Richardson DC, Benedict C, Ray PH (1984) J Med Chem 27:717–726PubMedGoogle Scholar
  13. Birck MR, Holler TP, Woodard RV (2000) J Am Chem Soc 122:9334–9335Google Scholar
  14. Bishop RE (2005) Mol Microbiol 57:900–912PubMedGoogle Scholar
  15. Black MT, Bruton G (1998) Curr Pharm Des 4:133–154PubMedGoogle Scholar
  16. Bodewits K, Raetz CRH, Govan JR, Campopiano DJ (2010) Antimicrob Agents Chemother 54:3531–3533PubMedGoogle Scholar
  17. Bozzoli A, Kazmierski W, Kennedy G, Paquarello A, Pecunioso A (2000) Bioorg Med Chem Lett 10:2759–2763PubMedGoogle Scholar
  18. Bush K, Bradford P (2007) In: Bonomo RA, Tolmasky ME (eds) Enzyme-mediated resistance to antibiotics: mechanisms, dissemination, and prospects for inhibition. ASM Press, Washington, DC, pp 67–80Google Scholar
  19. Brandish PE, Kimura K-I, Inukai M, Southgate R, Lonsdale JT, Bugg TDH (1996) Antimicrob Agents Chemother 40:1640–1644PubMedGoogle Scholar
  20. Breukink E, de Kruijff B (2006) Nat Rev Drug Discov 5:321–332PubMedGoogle Scholar
  21. Caroff M, Karibian D (2003) Carbohydr Res 338:2431–2447PubMedGoogle Scholar
  22. Chen H, Gartner E, Rolfe BG (1993) Appl Environ Microbiol 59:1058–1064PubMedGoogle Scholar
  23. Chen W, Huang YJ, Gundala SR, Yang H, Li M, Tai PC, Wang B (2010) Bioorg Med Chem 18:1617–25PubMedGoogle Scholar
  24. Cheng TJ, Sung MT, Liao HY, Chang YF, Chen CW, Huang CY, Chou LY, Wu YD, Chen YH, Cheng YS, Wong CH, Ma C, Cheng WC (2008) Proc Natl Acad Sci USA 105:431–436PubMedGoogle Scholar
  25. Claesson A, Luthman K, Gustafsson K, Bondesson G (1987) Biochem Biophys Res Commun 143:1063–1068PubMedGoogle Scholar
  26. Chimalakonda G, Ruiz N, Chng S-S, Garner RA, Kahne D, Silhavy TJ (2011) Proc Natl Acad Sci USA 108:2492–2497PubMedGoogle Scholar
  27. Clements JM, Coignard F, Johnson I, Chandler S, Palan S, Waller A, Wijkmans J, Hunter MG (2002) Antimicrob Agents Chemother 46:1793–1799PubMedGoogle Scholar
  28. Clementz T, Raetz CR (1991) J Biol Chem 266:9687–9696PubMedGoogle Scholar
  29. Cosloy SD (1973) J Bacteriol 114:679–684PubMedGoogle Scholar
  30. Davies JA, Anderson GK, Beveridge TJ, Clark HC (1983) J Bacteriol 156:837–845PubMedGoogle Scholar
  31. Davidson AL, Dassa E, Orelle C, Chen J (2008) Microbiol Mol Biol Rev 72:317–364PubMedGoogle Scholar
  32. De Leon GP, Elowe NH, Koteva KP, Valvano MA, Wright GD (2006) Chem Biol 13:437–441PubMedGoogle Scholar
  33. Derouaux A, Turk S, Olrichs NK, Gobec S, Breukink E, Amoroso A, Offant J, Bostock J, Mariner K, Chopra I, Vernet T, Zervosen A, Joris B, Frère JM, Nguyen-Distèche M, Terrak M (2011) Biochem Pharmacol 81:1098–1105PubMedGoogle Scholar
  34. Doerrler WT, Reedy MC, Raetz CR (2001) J Biol Chem 276:11461–11464PubMedGoogle Scholar
  35. Doerrler WT, Raetz CR (2002) J Biol Chem 277:36697–36705PubMedGoogle Scholar
  36. Doerrler WT, Gibbons HS, Raetz CR (2004) J Biol Chem 279:45102–45109PubMedGoogle Scholar
  37. Desroy N, Moreau F, Briet S, Le Fralliec G, Floquet S, Durant L, Vongsouthi V, Gerusz V, Denis A, Escaich S (2009) Bioorg Med Chem 17:1276–1289PubMedGoogle Scholar
  38. Dreier J (2007) In: Bonomo RA, Tolmasky ME (eds) Enzyme-mediated resistance to antibiotics: mechanisms, dissemination, and prospects for inhibition. ASM Press, Washington DC, pp 235–264Google Scholar
  39. Du S, Tsipori H, Baasov T (1997) Bioorg Med Chem Lett 7:2469–2472Google Scholar
  40. Durka M, Tikad A, Périon R, Bosco M, Andaloussi M, Floquet S, Malacain E, Moreau F, Oxoby M, Gerusz V, Vincent SP (2011) Chemistry 17:11305–11313PubMedGoogle Scholar
  41. Fletcher E, Fleiszig SMJ, Brannan NA (1993) Invest Ophthalmol Vis Sci 34:1930–1936PubMedGoogle Scholar
  42. García P, Arca P, Evaristo Suárez J (1995) Antimicrob Agents Chemother 39:1569–1573PubMedGoogle Scholar
  43. Gibbons HS, Kalb SR, Cotter RJ, Raetz CRH (2005) Mol Microbiol 55:425–440PubMedGoogle Scholar
  44. Goldman RC, Baizman ER, Branstrom AA, Longley CB (2000) Bioorg Med Chem Lett 10:2251–2254PubMedGoogle Scholar
  45. Goldman RC, Kohlbrenner WE, Lartey P, Pernet A (1987) Nature 329:162–164PubMedGoogle Scholar
  46. Gotoh N, Murata T, Ozaki T, Kimura T, Kondo A, Nishino T (2003) J Infect Chemother 9:101–103PubMedGoogle Scholar
  47. Gram HC (1884) Fortschr Med 2:185–189Google Scholar
  48. Gronenberg LS, Kahne D (2010) J Am Chem Soc 132:2518–2519PubMedGoogle Scholar
  49. Gronow S, Oertelt C, Ervela E, Zamyatina A, Kosma P, Skurnik M, Holst O (2001) J Endotoxin Res 7:263–270PubMedGoogle Scholar
  50. Helena Mäkelä P, Valtonen VV, Valtonen M (1973) J Infect Dis 128; Supplement: Bacterial lipopolysaccharides: chemistry, biology, and clinical significance of endotoxins. pp S81–S85Google Scholar
  51. Holtje JV (1998) Microbiol Mol Biol Rev 62:181–203PubMedGoogle Scholar
  52. Hu XE, Kim NK, Grinius L, Morris CM, Wallace CD, Mieling GE, Demuth TP Jr (2003) Synthesis 2003(11):1732–1738Google Scholar
  53. Hug I, Feldman MF (2011) Glycobiology 21:138–151PubMedGoogle Scholar
  54. Hunt JF, Weinkauf S, Henry L, Fak JJ, McNicholas P, Oliver DB, Deisenhofer J (2002) Science 297:2018–26PubMedGoogle Scholar
  55. Isono F, Katayama T, Inukai M, Haneishi T (1989) J Antibiot (Tokyo) 42:674–679Google Scholar
  56. Istivan TS, Coloe PJ (2006) Microbiology 152:1263–1274PubMedGoogle Scholar
  57. Jackman JE, Raetz CR, Fierke CA (1999) Biochemistry 38:1902–1911PubMedGoogle Scholar
  58. Jackman JE, Fierke CA, Tumey LN, Pirrung M, Uchiyama T, Tahir SH, Hindsgaul O, Raetz CRH (2000) J Biol Chem 275:11002–11009PubMedGoogle Scholar
  59. Kelly J, Jarrell H, Millar L, Tessier L, Fiori LM, Lau PC, Allan B, Szymanski CM (2006) J Bacteriol 188:2427–2434PubMedGoogle Scholar
  60. Kaderbhai N, Khan T (2008) Int J Pept Res Ther 14:173–178Google Scholar
  61. Kahan FM, Kahan JS, Cassidy PJ, Kropp H (1974) Ann N Y Acad Sci 235:364–86PubMedGoogle Scholar
  62. Kenne L, Lindberg B, Söderholm E, Bundle DR, Griffith DW, Morris JG (1983) Carbohydr Res 111:289–296PubMedGoogle Scholar
  63. Kido N, Torgov VI, Sugiyama T, Uchiya K, Sugihara H, Komatsu T, Kato N, Jann K (1995) J Bacteriol 177:2178–2187PubMedGoogle Scholar
  64. Kintz E, Goldberg JB (2008) Future Microbiol 3:191–203PubMedGoogle Scholar
  65. Kline T, Andersen NH, Harwood EA, Bowman J, Malanda A, Endsley S, Erwin A, Doyle M, Fong S, Harris A, Mendelsohn B, Mdluli K, Raetz CRH, Stover CK, Witte PR, Yabannavar A, Zhu S (2002) J Med Chem 45:3112–3129PubMedGoogle Scholar
  66. Kneidinger B, Graninger M, Puchberger M, Kosma P, Messner P (2001) J Biol Chem 276:20935–20944PubMedGoogle Scholar
  67. Kondo K, Doi H, Adachi H, Nishimura Y (2004) Bioorg Med Chem Lett 14:467–470PubMedGoogle Scholar
  68. Kuo DW, Chan K, Wilson CJ, Griffin PP, Williams H, Knight WB (1993) Arch Biochem Biophys 303:274–280PubMedGoogle Scholar
  69. Lee H, Hsu FF, Turk J, Groisman EA (2004) J Bacteriol 186:4124–4133PubMedGoogle Scholar
  70. Li M, Huang YJ, Tai PC, Wang B (2008) Biochem Biophys Res Commun 368:839–845PubMedGoogle Scholar
  71. Lindberg B, Lindh F, Lönngren J, Lindberg AA, Svenson SB (1981) Carbohydr Res 97:105–112PubMedGoogle Scholar
  72. Lior H (1994) Classification of Escherichia coli. In: Gyles CL (ed) Escherichia coli in domestic animals and humans. CAB International, UK, pp 31–72Google Scholar
  73. Liu D, Cole R, Reeves PR (1996) J Bacteriol 178:2102–2107PubMedGoogle Scholar
  74. Luthman K, Claesson A (1987) Carbohydr Res 166:233–251PubMedGoogle Scholar
  75. Malinverni JC, Silhavy TJ (2009) Proc Natl Acad Sci USA 106:8009–8014PubMedGoogle Scholar
  76. Mansoor UF, Vitharana D, Reddy PA, Daubaras DL, McNicholas P, Orth P, Black T, Siddiqui MA (2011) Bioorg Med Chem Lett 21:1155–1161PubMedGoogle Scholar
  77. Martinić M, Hoare A, Contreras I, Alvarez SA (2011) PLoS One 6:e25557, Epub 2011 Oct 3PubMedGoogle Scholar
  78. McDonald LA, Barbieri LR, Carter GT, Lenoy E, Lotvin J, Petersen PJ, Siegel MM, Singh G, Williamson RT (2001) J Am Chem Soc 124:10260–10261Google Scholar
  79. McGowan CC, Necheva A, Thompson SA, Cover TL, Blaser MJ (1998) Mol Microbiol 30:19–31PubMedGoogle Scholar
  80. Mochalkin I, Knaefels JD, Lightle S (2008) Protein Sci 17:450–457PubMedGoogle Scholar
  81. Mohammadi T, van Dam V, Sijbrandi R, Vernet T, Zapun A, Bouhss A, Diepeveen-de Bruin M, Nguyen-Disteche M, de Kruijff B, Breukink E (2011) EMBO J 30:1425–1432PubMedGoogle Scholar
  82. Mota-Meira M, LaPointe G, Lacroix C, Lavoie MC (2000) Antimicrob Agents Chemother 44:24–29PubMedGoogle Scholar
  83. Narita S, Tokuda H (2009) FEBS Lett 583:2160–2164PubMedGoogle Scholar
  84. Navas J, León J, Arroyo M, García Lobo JM (1990) Antimicrob Agents Chemother 34:2016–2018PubMedGoogle Scholar
  85. Nikaido H (1976) Biochim Biophys Acta 433:118–132PubMedGoogle Scholar
  86. Nikaido H, Vaara M (1985) Microbiol Rev 49:1–32PubMedGoogle Scholar
  87. Nikaido H (2003) Microbiol Mol Biol Rev 67:593–656PubMedGoogle Scholar
  88. Norbeck DW, Rosenbrook W, Kramer JB, Grampovnik DJ, Lartey PA (1989) J Med Chem 32:625–629PubMedGoogle Scholar
  89. Nouwen N, Driessen AJ (2002) Mol Microbiol 44:1397–1405PubMedGoogle Scholar
  90. Ochs MM, McCusker MP, Bains M, Hancock REW (1999) Antimicrob Agents Chemother 43:1085–1090PubMedGoogle Scholar
  91. Onishi HR, Pelak BA, Gerckens LS, Silver LL, Kahan FM, Chen MH, Patchett AA, Galloway SM, Hyland SA, Anderson MA, Raetz CRH (1996) Science 274:980–982PubMedGoogle Scholar
  92. Olesky M, Zhao S, Rosenberg RL, Nicholas RA (2006) J Bacteriol 188:2300–2308PubMedGoogle Scholar
  93. Osborne AR, Rapoport TA (2007) Cell 129:97–110PubMedGoogle Scholar
  94. Ostash B, Walker S (2010) Nat Prod Rep 27:1594–1617PubMedGoogle Scholar
  95. Page MGP (2007) In: Bonomo RA, Tolmasky M (eds) Enzyme-mediated resistance to antibiotics: mechanisms, dissemination and prospects for inhibition. ASM Press, Washington DC, pp 81–100Google Scholar
  96. Page MGP, Dantier C, Desarbre E (2010) Antimicrob Agents Chemother 54:2291–2302PubMedGoogle Scholar
  97. Pai H, Kim J-W, Kim J, Lee JH, Choe KW, Gotoh N (2001) Antimicrob Agents Chemother 45:480–484PubMedGoogle Scholar
  98. Palomar J, Puig M, Montilla R, Loren JG, Vinas M (1995) Microbios 82:21–26PubMedGoogle Scholar
  99. Parr TR Jr, Moore RA, Moore LV, Hancock RE (1987) Antimicrob Agents Chemother 31:121–123PubMedGoogle Scholar
  100. Perry MB, MacLean L, Griffith DW (1986) Biochem Cell Biol 64:21–28PubMedGoogle Scholar
  101. Popoff MY, Minor LL (1997) Antigenic formulas of the Salmonella serovars, 7th revision. WHO Collaborating Centre for Reference and Research on Salmonella. Institut Pasteur.Google Scholar
  102. Raetz CRH (1993) J Bacteriol 175:5745–5753PubMedGoogle Scholar
  103. Raymond CK, Sims EH, Kas A, Spencer DH, Kutyavin TV, Ivey RG, Zhou Y, Kaul R, Clendenning JB, Olson MV (2002) J Bacteriol 184:3614–3622PubMedGoogle Scholar
  104. Rees DC, Johnson E, Lewinson O (2009) Nat Rev Mol Cell Biol 10:218–227PubMedGoogle Scholar
  105. Reeves PR, Hobbs M, Valvano M, Skurnik M, Whitfield C, Coplin D, Kido N, Klena J, Maskell D, Raetz C, Rick P (1996) Trends Microbiol 4:495–503PubMedGoogle Scholar
  106. Reizer J, Reizer A, Saier MH (1992) Protein Sci 1:1326–1332PubMedGoogle Scholar
  107. Rigsby R, Fillgrove K, Beihoffer L, Armstrong R (2005) Methods Enzymol 401:367–379PubMedGoogle Scholar
  108. Roberts TC, Smith PA, Cirz RT, Romesberg FE (2007) J Am Chem Soc 129:15830–15838PubMedGoogle Scholar
  109. Ruiz N, Gronenberg LS, Kahne D, Silhavy TJ (2008) Proc Natl Acad Sci USA 105:5537–5542PubMedGoogle Scholar
  110. Ruiz N, Kahne D, Silhavy TJ (2006) Nat Rev Microbiol 4:57–64PubMedGoogle Scholar
  111. Ruiz N, Montero T, Hernandez-Borrell J, Viñas M (2003) Microb Drug Resist 9:257–264PubMedGoogle Scholar
  112. Russell RRB (1972) J Bacteriol 111:622–624PubMedGoogle Scholar
  113. Samuel G, Reeves P (2003) Carbohydr Res 338:2503–2519PubMedGoogle Scholar
  114. Sheffer-Dee-Noor S, Belakhov V, Baasov T (1993) Biorg Med Chem Lett 3:1583–1588Google Scholar
  115. Sofia MJ, Allanson N, Hatzenbuhler NT, Jain R, Kakarla R, Kogan N, Liang R, Liu D, Silva DJ, Wang H, Gange D, Anderson J, Chen A, Chi F, Dulina R, Huang B, Kamau M, Wang C, Baizman E, Branstrom A, Bristo N, Goldman R, Han K, Longley C, Midha S, Axelrod HR (1999) J Med Chem 42:3193–3198PubMedGoogle Scholar
  116. Sperandeo P, Villa R, Martorana AM, Šamalikova M, Grandori R, Dehò G, Polissi A (2011) J Bacteriol 193:1042–1053PubMedGoogle Scholar
  117. Srinivars N, Jetter P, Ueberbacher BJ, Werneburg M, Zerbe K, Steinmann J, Van der Meijden B, Bernadini F, Lederer A, Dias RLA, Misson PE, Henze H, Zumbrunn J, Gombert FO, Obrecht D, Hunziker P, Schauer S, Ziegler U, Käch A, Eberl L, Riedel K, DeMarco SJ, Robinson JA (2010) Science 327:1010–1013Google Scholar
  118. Stachyra T, Dini C, Ferrari P, Bouhss A, Heijenoort J, Mengin-Lecreulx D, Blanot D, Biton J, Le Beller D (2004) Antimicrob Agents Chemother 48:897–902PubMedGoogle Scholar
  119. Stephens C, Shapiro L (1997) Chem Biol 4:637–641PubMedGoogle Scholar
  120. Stone KJ, Strominger JL (1971) Proc Natl Acad Sci 68:3223–3227PubMedGoogle Scholar
  121. Sugie Y, Inagaki S, Kato Y, Nishida H, Pang CH, Saito T, Sakemi S, Dib-Hajj F, Mueller JP, Sutcliffe J, Kojima Y (2002) J Antibiot (Tokyo) 55:25–9Google Scholar
  122. Takeda S, Nakai T, Wakai Y, Ikeda F, Hatano K (2007) Antimicrob Agents Chemother 51:826–830PubMedGoogle Scholar
  123. Thomsen LE, Chadfield MS, Bispham J, Wallis TS, Olsen JE (2003) FEMS Microbiol Lett 228:225–231PubMedGoogle Scholar
  124. Thuruthyil SJ, Zhu H, Willcox MD (2001) Clin Experiment Opthalmol 29:147–149Google Scholar
  125. Touzé T, Tran AX, Hankins JV, Mengin-Lecreuix D, Trent MS (2008) Mol Microbiol 67:264–277PubMedGoogle Scholar
  126. Trent MS, Raetz CRH (2002) J Endotoxin Res 8:158Google Scholar
  127. Ulaganathan V, Buetow L, Hunter WN (2007) J Mol Biol 369:305–312PubMedGoogle Scholar
  128. Vaara M (1993) Antimicrob Agents Chemother 37:354–356PubMedGoogle Scholar
  129. Valvano MA, Messner P, Kosma P (2002) Microbiology 148:1979–1989PubMedGoogle Scholar
  130. Van Heijenoort Y, Leduc M, Singer H, Van Heijenoort J (1987) J Gen Microbiol 133:667–674PubMedGoogle Scholar
  131. Vila J, Marti S, Sánchez-Céspedes J (2007) J Antimicrob Chemother 59:1210–1215, jac.oxfordjournals.orgPubMedGoogle Scholar
  132. Vuorio R, Vaara M (1992) Antimicrob Agents Chemother 36:826–829PubMedGoogle Scholar
  133. Whitfield C, Amor PA, Köplin R (1997) Mol Microbiol 23:629–638PubMedGoogle Scholar
  134. Whittington DA, Rusche KM, Shin H, Fierke CA, Christianson DW (2003) Proc Natl Acad Sci 100:8146–8150PubMedGoogle Scholar
  135. Wilkinson SG (1996) Prog Lipid Res 35:283–343PubMedGoogle Scholar
  136. Williams AH, Immormino RM, Gewirth DT, Raetz CRH (2006) Proc Natl Acad Sci USA 103:10877–10882PubMedGoogle Scholar
  137. Wyckoff TJO, Raetz CRH, Jackman JE (1998) Trends Microbiol 6:154–159PubMedGoogle Scholar
  138. Yamamoto S, Miyake K, Koike Y, Watanabe M, Machida Y, Ohta M, Iijima S (1999) J Bacteriol 181:5176–5184PubMedGoogle Scholar
  139. Yan A, Guan Z, Raetz CRH (2007) J Biol Chem 282:36077–36089PubMedGoogle Scholar
  140. Yuan J, Zhang ZZ, Chen XZ, Yang W, Huan LD (2004) Appl Microbiol Biotechnol 67:444–452Google Scholar
  141. Zamyatina A, Gronow S, Oertelt C, Puchberger M, Brade H, Kosma P (2000) Angew Chem Int 39:4150–4153Google Scholar

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© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Basilea Pharmaceutica International LtdBaselSwitzerland

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