Display options
Share it on

Front Microbiol. 2011 Nov 22;2:232. doi: 10.3389/fmicb.2011.00232. eCollection 2011.

Exploring the pharmacological potential of promiscuous host-defense peptides: from natural screenings to biotechnological applications.

Frontiers in microbiology

Osmar N Silva, Kelly C L Mulder, Aulus E A D Barbosa, Anselmo J Otero-Gonzalez, Carlos Lopez-Abarrategui, Taia M B Rezende, Simoni C Dias, Octávio L Franco

Affiliations

  1. Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Centro de Análises Protômicas e Bioquímicas, Universidade Católica de Brasília Brasília, Brazil.

PMID: 22125552 PMCID: PMC3222093 DOI: 10.3389/fmicb.2011.00232

Abstract

In the last few years, the number of bacteria with enhanced resistance to conventional antibiotics has dramatically increased. Most of such bacteria belong to regular microbial flora, becoming a real challenge, especially for immune-depressed patients. Since the treatment is sometimes extremely expensive, and in some circumstances completely inefficient for the most severe cases, researchers are still determined to discover novel compounds. Among them, host-defense peptides (HDPs) have been found as the first natural barrier against microorganisms in nearly all living groups. This molecular class has been gaining attention every day for multiple reasons. For decades, it was believed that these defense peptides had been involved only with the permeation of the lipid bilayer in pathogen membranes, their main target. Currently, it is known that these peptides can bind to numerous targets, as well as lipids including proteins and carbohydrates, from the surface to deep within the cell. Moreover, by using in vivo models, it was shown that HDPs could act both in pathogens and cognate hosts, improving immunological functions as well as acting through multiple pathways to control infections. This review focuses on structural and functional properties of HDP peptides and the additional strategies used to select them. Furthermore, strategies to avoid problems in large-scale manufacture by using molecular and biochemical techniques will also be explored. In summary, this review intends to construct a bridge between academic research and pharmaceutical industry, providing novel insights into the utilization of HDPs against resistant bacterial strains that cause infections in humans.

Keywords: antimicrobials; host-defense peptides; innate immunity; microbial infections

References

  1. Bioorg Med Chem Lett. 2008 Jul 15;18(14):4038-43 - PubMed
  2. Burns. 1999 Aug;25(5):411-3 - PubMed
  3. Trends Immunol. 2009 Mar;30(3):131-41 - PubMed
  4. Methods Mol Biol. 2008;494:9-29 - PubMed
  5. Cell Mol Life Sci. 2011 Jul;68(13):2189-99 - PubMed
  6. N Engl J Med. 2009 Jan 29;360(5):439-43 - PubMed
  7. Nat Protoc. 2008;3(2):163-75 - PubMed
  8. Biochim Biophys Acta. 2006 Sep;1758(9):1393-407 - PubMed
  9. Gut. 2002 Sep;51(3):356-61 - PubMed
  10. Biotechnol Appl Biochem. 2009 Jul 06;54(1):1-9 - PubMed
  11. Drug Discov Today. 2007 Nov;12(21-22):966-71 - PubMed
  12. Plant J. 2005 Mar;41(5):767-78 - PubMed
  13. Peptides. 2010 Nov;31(11):1957-65 - PubMed
  14. J Neuroimmunol. 1998 Apr 1;84(1):53-60 - PubMed
  15. Comb Chem High Throughput Screen. 2005 May;8(3):219-33 - PubMed
  16. Methods Mol Biol. 2010;618:267-85 - PubMed
  17. Curr Opin Plant Biol. 2009 Aug;12(4):406-13 - PubMed
  18. Science. 2010 May 28;328(5982):1168-72 - PubMed
  19. J Dairy Sci. 2009 Dec;92(12):6046-51 - PubMed
  20. Am J Respir Crit Care Med. 2008 Feb 1;177(3):279-84 - PubMed
  21. Protein Expr Purif. 2011 Dec;80(2):260-7 - PubMed
  22. Curr Protein Pept Sci. 2010 May;11(3):181-8 - PubMed
  23. Scand J Clin Lab Invest. 2010 Apr 19;70(3):194-200 - PubMed
  24. FASEB J. 2010 May;24(5):1320-34 - PubMed
  25. Biochim Biophys Acta. 2010 Feb;1798(2):105-13 - PubMed
  26. Plant Physiol Biochem. 2008 Nov;46(11):941-50 - PubMed
  27. Antimicrob Agents Chemother. 2002 Jan;46(1):101-4 - PubMed
  28. J Bacteriol. 2005 May;187(9):2983-91 - PubMed
  29. Anal Biochem. 2005 Nov 15;346(2):258-67 - PubMed
  30. Antimicrob Agents Chemother. 2010 Sep;54(9):4003-5 - PubMed
  31. Biosci Rep. 2009 Nov 10;30(2):101-9 - PubMed
  32. J Exp Bot. 2008;59(3):501-20 - PubMed
  33. Trends Immunol. 2002 Jun;23(6):291-6 - PubMed
  34. J Immunol. 2002 Mar 15;168(6):3024-32 - PubMed
  35. Clin Immunol Immunopathol. 1991 Aug;60(2):310-8 - PubMed
  36. Biopolymers. 2010;94(5):617-25 - PubMed
  37. Biochemistry. 2008 May 20;47(20):5581-9 - PubMed
  38. Mol Biol Rep. 2011 Jan;38(1):429-36 - PubMed
  39. Burns. 2006 Jun;32(4):402-7 - PubMed
  40. FEMS Microbiol Lett. 2008 Dec;289(2):126-9 - PubMed
  41. Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14614-9 - PubMed
  42. Regul Pept. 2010 Nov 30;165(1):102-10 - PubMed
  43. Acta Pharmacol Toxicol (Copenh). 1973;33(5):400-8 - PubMed
  44. Int Immunopharmacol. 2003 Feb;3(2):247-56 - PubMed
  45. J Microbiol Methods. 2008 Dec;75(3):425-31 - PubMed
  46. Chem Biol. 2006 Oct;13(10):1101-7 - PubMed
  47. Antimicrob Agents Chemother. 2003 Aug;47(8):2464-70 - PubMed
  48. Exp Parasitol. 2009 Jul;122(3):247-9 - PubMed
  49. Acta Trop. 2009 Feb;109(2):163-6 - PubMed
  50. FEBS Lett. 2011 Apr 6;585(7):995-1000 - PubMed
  51. Biotechnol Adv. 2010 Jul-Aug;28(4):427-35 - PubMed
  52. Expert Opin Drug Discov. 2009 Jun;4(6):659-71 - PubMed
  53. Ann Clin Microbiol Antimicrob. 2011 Mar 22;10:11 - PubMed
  54. Peptides. 2011 Feb;32(2):353-7 - PubMed
  55. FEBS J. 2009 Nov;276(22):6497-508 - PubMed
  56. J Leukoc Biol. 2001 May;69(5):691-7 - PubMed
  57. Methods Mol Biol. 2008;494:127-59 - PubMed
  58. J Immunol. 2009 Nov 1;183(9):5788-98 - PubMed
  59. Protein Cell. 2010 Feb;1(2):143-52 - PubMed
  60. Curr Protein Pept Sci. 2010 May;11(3):210-9 - PubMed
  61. Protein Expr Purif. 2002 Aug;25(3):372-8 - PubMed
  62. PLoS Pathog. 2010 Oct 28;6(10):e1001067 - PubMed
  63. Methods Mol Biol. 2010;618:137-54 - PubMed
  64. J Agric Food Chem. 2011 Feb 23;59(4):1145-51 - PubMed
  65. Can J Vet Res. 2006 Oct;70(4):243-50 - PubMed
  66. Plant Signal Behav. 2009 Jun;4(6):489-92 - PubMed
  67. Shock. 2008 Aug;30(2):117-26 - PubMed
  68. Eur J Biochem. 1996 Feb 1;235(3):516-25 - PubMed
  69. Protein Expr Purif. 2004 Jul;36(1):11-8 - PubMed
  70. Anesthesiology. 2007 Sep;107(3):437-41 - PubMed
  71. Peptides. 2005 Nov;26(11):2086-92 - PubMed
  72. J Nat Prod. 1994 Dec;57(12):1619-25 - PubMed
  73. Peptides. 2008 Jul;29(7):1085-93 - PubMed
  74. Science. 2002 Nov 1;298(5595):1025-9 - PubMed
  75. Nat Biotechnol. 2000 Feb;18(2):225-7 - PubMed
  76. Cell Mol Life Sci. 2010 Jun;67(12):2107-18 - PubMed
  77. J Immunol. 2005 Apr 1;174(7):4271-8 - PubMed
  78. Plant J. 2006 Feb;45(4):616-29 - PubMed
  79. J Immunol. 2001 Sep 15;167(6):3329-38 - PubMed
  80. Peptides. 2009 Dec;30(12):2089-94 - PubMed
  81. Biotechnol Bioeng. 2011 Mar;108(3):572-81 - PubMed
  82. Plant Biotechnol J. 2010 Jun;8(5):638-54 - PubMed
  83. J Pept Sci. 2006 Oct;12(10):643-52 - PubMed
  84. Curr Opin Pharmacol. 2009 Oct;9(5):580-8 - PubMed
  85. Antimicrob Agents Chemother. 1999 Jun;43(6):1317-23 - PubMed
  86. Bull World Health Organ. 2001;79(8):780-90 - PubMed
  87. J Biol Chem. 2001 Jun 22;276(25):22875-82 - PubMed
  88. Antimicrob Agents Chemother. 2005 May;49(5):1727-32 - PubMed
  89. J Pept Sci. 2006 May;12(5):341-6 - PubMed
  90. Biochem Pharmacol. 2004 Oct 1;68(7):1297-307 - PubMed
  91. Br J Dermatol. 2009 Feb;160(2):243-9 - PubMed
  92. Appl Environ Microbiol. 2007 Feb;73(3):939-46 - PubMed
  93. Br J Dermatol. 2010 Jul;163(1):121-7 - PubMed
  94. Immunobiology. 2006;211(4):315-22 - PubMed
  95. Cell Mol Life Sci. 2011 Jul;68(13):2161-76 - PubMed
  96. Methods Mol Biol. 2010;618:15-30 - PubMed
  97. Biomacromolecules. 2010 Jan 11;11(1):60-7 - PubMed
  98. Plant Cell Environ. 2011 Sep;34(9):1443-53 - PubMed
  99. Nat Biotechnol. 2005 Aug;23(8):1008-12 - PubMed
  100. Peptides. 2009 May;30(5):1007-20 - PubMed
  101. Comb Chem High Throughput Screen. 2005 May;8(3):257-72 - PubMed
  102. Arch Immunol Ther Exp (Warsz). 2010 Oct;58(5):365-77 - PubMed
  103. Eur J Immunol. 2007 Feb;37(2):434-44 - PubMed
  104. J Struct Funct Genomics. 2004;5(1-2):75-86 - PubMed
  105. Nat Biotechnol. 2006 Dec;24(12):1551-7 - PubMed
  106. J Pept Sci. 2008 Jan;14(1):110-4 - PubMed
  107. Antimicrob Agents Chemother. 2006 Oct;50(10):3330-5 - PubMed
  108. Peptides. 2011 May;32(5):929-37 - PubMed
  109. Int J Antimicrob Agents. 2010 Apr;35(4):410-1 - PubMed
  110. Eur J Immunol. 2001 Apr;31(4):1066-75 - PubMed
  111. Nature. 2002 Jan 24;415(6870):389-95 - PubMed
  112. Bioeng Bugs. 2010 May-Jun;1(3):217-20 - PubMed
  113. Methods Mol Biol. 2010;618:125-33 - PubMed
  114. J Neuroimmunol. 2008 Aug 30;200(1-2):11-6 - PubMed
  115. Antimicrob Agents Chemother. 2005 Jul;49(7):2665-72 - PubMed
  116. Inflamm Bowel Dis. 2010 Sep;16(9):1488-95 - PubMed
  117. Antimicrob Agents Chemother. 2007 Jun;51(6):2005-10 - PubMed
  118. FEBS J. 2009 Nov;276(22):6483-96 - PubMed
  119. J Invest Dermatol. 2008 Jun;128(6):1525-34 - PubMed
  120. Biopolymers. 1998;47(6):479-91 - PubMed
  121. Curr Pharm Des. 2010;16(28):3204-11 - PubMed
  122. J Immunol. 2006 Feb 15;176(4):2455-64 - PubMed
  123. Nat Rev Immunol. 2003 Sep;3(9):710-20 - PubMed
  124. ACS Chem Biol. 2010 Oct 15;5(10):905-17 - PubMed
  125. Protein Expr Purif. 2007 Sep;55(1):175-82 - PubMed
  126. Biochim Biophys Acta. 1999 Dec 15;1462(1-2):1-10 - PubMed
  127. Insect Biochem Mol Biol. 2005 Dec;35(12):1335-46 - PubMed
  128. Toxicon. 2010 Dec 15;56(7):1092-102 - PubMed
  129. FASEB J. 2010 Sep;24(9):3232-8 - PubMed
  130. J Infect Dis. 2007 Nov 1;196(9):1425-30 - PubMed

Publication Types