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The Journal of antimicrobial chemotherapy
05 01, 2017;72 (5): 1275-1284.

DNA replication proteins as potential targets for antimicrobials in drug-resistant bacterial pathogens.

Erika van Eijk, Bert Wittekoek, Ed J Kuijper, Wiep Klaas Smits
Author Information
PMID: 28073967 DOI: 10.1093/jac/dkw548

Abstract

With the impending crisis of antimicrobial resistance, there is an urgent need to develop novel antimicrobials to combat difficult infections and MDR pathogenic microorganisms. DNA replication is essential for cell viability and is therefore an attractive target for antimicrobials. Although several antimicrobials targeting DNA replication proteins have been developed to date, gyrase/topoisomerase inhibitors are the only class widely used in the clinic. Given the numerous essential proteins in the bacterial replisome that may serve as a potential target for inhibitors and the relative paucity of suitable compounds, it is evident that antimicrobials targeting the replisome are underdeveloped so far. In this review, we report on the diversity of antimicrobial compounds targeting DNA replication and highlight some of the challenges in developing new drugs that target this process.

References

  1. Antimicrob Agents Chemother. 2001 Dec;45(12):3544-7 [PMID: 11709337]
  2. Trends Microbiol. 2014 Aug;22(8):438-45 [PMID: 24842194]
  3. Antimicrob Agents Chemother. 2000 Aug;44(8):2160-5 [PMID: 10898691]
  4. Antimicrob Agents Chemother. 2005 Mar;49(3):987-95 [PMID: 15728893]
  5. Curr Enzym Inhib. 2011 Oct;7(3):147-153 [PMID: 22844265]
  6. J Biol Chem. 2009 Jun 26;284(26):17365-9 [PMID: 19329793]
  7. Gene. 1992 Feb 1;111(1):43-9 [PMID: 1312503]
  8. Antimicrob Agents Chemother. 2012 Sep;56(9):4786-92 [PMID: 22733075]
  9. Antimicrob Agents Chemother. 2016 May 23;60(6):3626-32 [PMID: 27044547]
  10. Curr Pharm Des. 2013;19(26):4673 [PMID: 23260027]
  11. Bioorg Med Chem Lett. 2009 Feb 1;19(3):800-2 [PMID: 19109016]
  12. ChemMedChem. 2008 Oct;3(10):1604-15 [PMID: 18792034]
  13. Bioorg Med Chem Lett. 2011 Aug 1;21(15):4556-60 [PMID: 21719282]
  14. Antimicrob Agents Chemother. 2000 Aug;44(8):2217-21 [PMID: 10898708]
  15. Antimicrob Agents Chemother. 2011 Mar;55(3):1088-96 [PMID: 21189350]
  16. J Infect Dis. 2008 Feb 1;197(3):435-8 [PMID: 18199029]
  17. Med Res Rev. 2004 Jul;24(4):475-528 [PMID: 15170593]
  18. Curr Top Med Chem. 2009;9(11):981-98 [PMID: 19747119]
  19. Chem Biol. 2005 May;12(5):595-604 [PMID: 15911380]
  20. Nucleic Acids Res. 2014 Feb;42(3):1393-413 [PMID: 24106089]
  21. J Antimicrob Chemother. 2015 Jan;70(1):182-9 [PMID: 25190720]
  22. EMBO J. 1996 Mar 15;15(6):1412-20 [PMID: 8635474]
  23. Antimicrob Agents Chemother. 2015;59(6):3474-81 [PMID: 25845866]
  24. Bioorg Med Chem Lett. 2006 Mar 1;16(5):1286-90 [PMID: 16343901]
  25. Nat Struct Mol Biol. 2010 Sep;17(9):1152-3 [PMID: 20802486]
  26. Am J Med. 2011 Nov;124(11):1081.e1-7 [PMID: 21944159]
  27. J Med Chem. 2006 Feb 23;49(4):1455-65 [PMID: 16480282]
  28. Antimicrob Agents Chemother. 2014;58(4):2387-92 [PMID: 24514098]
  29. Nucleic Acids Res. 1990 Dec 25;18(24):7381-7 [PMID: 2259629]
  30. Biochemistry. 2014 Mar 18;53(10):1565-74 [PMID: 24576155]
  31. Nature. 2010 Aug 19;466(7309):935-40 [PMID: 20686482]
  32. Antimicrob Agents Chemother. 2014 May;58(5):2657-64 [PMID: 24566174]
  33. Expert Opin Ther Pat. 2010 Oct;20(10):1295-319 [PMID: 20645884]
  34. Nat Genet. 2013 Jan;45(1):109-13 [PMID: 23222960]
  35. Nat Commun. 2014;5:3114 [PMID: 24445449]
  36. Antimicrob Agents Chemother. 2008 Sep;52(9):3339-49 [PMID: 18625781]
  37. Bioorg Med Chem Lett. 2007 May 15;17(10):2723-7 [PMID: 17368897]
  38. Antimicrob Agents Chemother. 2013 Aug;57(8):4039-41 [PMID: 23689716]
  39. N Engl J Med. 2005 Dec 8;353(23):2433-41 [PMID: 16322603]
  40. Bioorg Med Chem Lett. 2006 Feb 15;16(4):891-6 [PMID: 16298129]
  41. Curr Opin Microbiol. 2014 Feb;17:67-74 [PMID: 24581695]
  42. Bioorg Med Chem Lett. 2012 Jan 1;22(1):85-9 [PMID: 22154350]
  43. Expert Opin Drug Discov. 2009 Dec 1;4(12):1281-1294 [PMID: 20354588]
  44. Infect Disord Drug Targets. 2012 Oct;12(5):327-31 [PMID: 23017159]
  45. Clin Infect Dis. 2005 Jul 15;41 Suppl 2:S120-6 [PMID: 15942878]
  46. Bioorg Med Chem Lett. 2011 Jul 15;21(14):4197-202 [PMID: 21684746]
  47. Biochem Pharmacol. 2012 Sep 1;84(5):654-60 [PMID: 22743594]
  48. Proc Natl Acad Sci U S A. 2010 Jan 12;107(2):633-8 [PMID: 20018747]
  49. Nucleic Acids Res. 2002 May 15;30(10):2144-53 [PMID: 12000834]
  50. PLoS Pathog. 2009 Nov;5(11):e1000663 [PMID: 19936046]
  51. Bioorg Med Chem Lett. 2005 Feb 1;15(3):729-32 [PMID: 15664846]
  52. PLoS One. 2015 Mar 26;10(3):e0119760 [PMID: 25811866]
  53. Lancet Infect Dis. 2014 Apr;14(4):327-40 [PMID: 24670627]
  54. Cell. 1990 Oct 19;63(2):393-404 [PMID: 2170028]
  55. Antimicrob Agents Chemother. 2014 Oct;58(10):5714-8 [PMID: 25022586]
  56. Biopolymers. 2016 Aug;105(8):532-46 [PMID: 26918303]
  57. J Biol Chem. 1984 Jul 25;259(14):9199-201 [PMID: 6086626]
  58. J Med Chem. 2003 Jun 19;46(13):2731-9 [PMID: 12801236]
  59. Cell. 2006 Feb 24;124(4):837-48 [PMID: 16497592]
  60. Lancet Infect Dis. 2001 Sep;1(2):101-14 [PMID: 11871461]
  61. Appl Microbiol Biotechnol. 2011 Nov;92(3):479-97 [PMID: 21904817]
  62. Antimicrob Agents Chemother. 2014;58(2):1187-91 [PMID: 24247123]
  63. Microbiology. 2010 Nov;156(Pt 11):3354-9 [PMID: 20724385]
  64. Methods Mol Biol. 2012;922:1-21 [PMID: 22976174]
  65. Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1:4639-44 [PMID: 20616009]
  66. ACS Chem Biol. 2014 Sep 19;9(9):2023-31 [PMID: 24992706]
  67. PLoS One. 2013;8(3):e58765 [PMID: 23536821]
  68. Genes Dev. 2001 Mar 15;15(6):748-61 [PMID: 11274059]
  69. J Med Microbiol. 2008 Jun;57(Pt 6):784-9 [PMID: 18480338]
  70. Antimicrob Agents Chemother. 2002 Dec;46(12):3770-5 [PMID: 12435675]
  71. Proc Natl Acad Sci U S A. 1978 Oct;75(10):4838-42 [PMID: 368801]
  72. Antimicrob Agents Chemother. 2012 Mar;56(3):1624-6 [PMID: 22203600]
  73. Expert Opin Drug Discov. 2010 Sep;5(9):883-902 [PMID: 22823262]
  74. Antimicrob Agents Chemother. 1994 Mar;38(3):409-14 [PMID: 8203832]
  75. Ann Inst Pasteur Microbiol. 1987 Nov-Dec;138(6):737-44 [PMID: 3135829]
  76. Open Biol. 2016 Dec;6(12 ):null [PMID: 28003473]
  77. Cold Spring Harb Perspect Biol. 2013 Apr 01;5(4):a010165 [PMID: 23545418]
  78. J Antibiot (Tokyo). 2014 Jan;67(1):7-22 [PMID: 23756684]
  79. Antimicrob Agents Chemother. 2007 Aug;51(8):2888-97 [PMID: 17548501]
  80. Curr Opin Pharmacol. 2014 Oct;18:76-83 [PMID: 25271174]
  81. Antimicrob Agents Chemother. 2007 Jan;51(1):119-27 [PMID: 17074800]
  82. Curr Drug Targets. 2012 Mar;13(3):352-72 [PMID: 22206257]
  83. Crit Rev Biochem Mol Biol. 2008 Sep-Oct;43(5):289-318 [PMID: 18937104]
  84. Adv Appl Bioinform Chem. 2015 Dec 08;8:49-63 [PMID: 26677339]
  85. Expert Opin Drug Discov. 2012 Apr;7(4):327-39 [PMID: 22458504]
  86. N Engl J Med. 2011 Feb 3;364(5):422-31 [PMID: 21288078]
  87. Nat Chem Biol. 2008 Nov;4(11):682-90 [PMID: 18936753]
  88. FEMS Microbiol Lett. 2008 Apr;281(2):210-4 [PMID: 18312360]
  89. Cell Mol Life Sci. 2010 Jun;67(12 ):2001-24 [PMID: 20165898]
  90. ACS Med Chem Lett. 2011 Apr 14;2(4):289-292 [PMID: 21552338]
  91. Antimicrob Agents Chemother. 1999 Aug;43(8):1982-7 [PMID: 10428923]
  92. Bull Soc Chim Fr. 1971 Jun;6:2349-56 [PMID: 5568642]
  93. Chem Biol. 2011 Aug 26;18(8):955-65 [PMID: 21867911]
  94. Science. 2015 Jun 5;348(6239):1106-12 [PMID: 26045430]
  95. J Antimicrob Chemother. 2003 May;51(5):1109-17 [PMID: 12697644]
  96. J Med Chem. 2005 Nov 3;48(22):7063-74 [PMID: 16250666]
  97. Antimicrob Agents Chemother. 1997 Feb;41(2):471-4 [PMID: 9021211]
  98. Proc Natl Acad Sci U S A. 1976 Nov;73(11):3872-6 [PMID: 186775]
  99. Proc Natl Acad Sci U S A. 1970 Nov;67(3):1454-61 [PMID: 4992015]
  100. Genes Dev. 1997 Oct 1;11(19):2580-92 [PMID: 9334322]
  101. Nat Rev Dis Primers. 2016 Apr 07;2:16020 [PMID: 27158839]
  102. Bioorg Med Chem Lett. 2012 Nov 1;22(21):6705-11 [PMID: 23006603]

MeSH Term

Anti-Bacterial Agents
Bacteria
Bacterial Proteins
DNA Replication
Drug Design
Drug Resistance, Multiple, Bacterial
Humans
Topoisomerase II Inhibitors

Chemicals

Anti-Bacterial Agents
Bacterial Proteins
Topoisomerase II Inhibitors
Journal Article Review Research Support, Non-U.S. Gov't
Article has an altmetric score of 6

Word Cloud

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