N-terminal Myristoylation Enhanced the Antimicrobial Activity of Antimicrobial Peptide PMAP-36PW.

Yongqing Liu, Shengnan Li, Tengfei Shen, Liangliang Chen, Jiangfei Zhou, Shuaibing Shi, Yang Wang, Zhanqin Zhao, Chengshui Liao, Chen Wang
Author Information
  1. Yongqing Liu: The Key Lab of Veterinary Biological Products, Henan University of Science and Technology, Luoyang, China.
  2. Shengnan Li: Department of Animal Science, University of Manitoba, Winnipeg, MB, Canada.
  3. Tengfei Shen: The Key Lab of Veterinary Biological Products, Henan University of Science and Technology, Luoyang, China.
  4. Liangliang Chen: The Key Lab of Veterinary Biological Products, Henan University of Science and Technology, Luoyang, China.
  5. Jiangfei Zhou: The Key Lab of Veterinary Biological Products, Henan University of Science and Technology, Luoyang, China.
  6. Shuaibing Shi: The Key Lab of Veterinary Biological Products, Henan University of Science and Technology, Luoyang, China.
  7. Yang Wang: Henan Provincial Open Laboratory of Key Disciplines in Environment and Animal Products Safety, Henan University of Science and Technology, Luoyang, China.
  8. Zhanqin Zhao: The Key Lab of Veterinary Biological Products, Henan University of Science and Technology, Luoyang, China.
  9. Chengshui Liao: Henan Provincial Open Laboratory of Key Disciplines in Environment and Animal Products Safety, Henan University of Science and Technology, Luoyang, China.
  10. Chen Wang: The Key Lab of Veterinary Biological Products, Henan University of Science and Technology, Luoyang, China.

Abstract

Drug-resistant bacteria infections and drug residues have been increasing and causing antibiotic resistance and public health threats worldwide. Antimicrobial peptides (AMPs) are novel antimicrobial drugs with the potential to solve these problems. Here, a peptide based on our previously studied peptide PMAP-36PW was designed via N-terminal myristoylation and referred to as Myr-36PW. The fatty acid modification provided the as-prepared peptide with good stability and higher antimicrobial activity compared with PMAP-36PW . Moreover, Myr-36PW exhibited effective anti-biofilm activity against Gram-negative bacteria and may kill bacteria by improving the permeability of their membranes. In addition, the designed peptide Myr-36PW could inhibit the bacterial growth of ATCC 25923 and GIM 1.551 to target organs, decrease the inflammatory damage, show an impressive therapeutic effect on mouse pneumonia and peritonitis experiments, and promote abscess reduction and wound healing in infected mice. These results reveal that Myr-36PW is a promising antimicrobial agent against bacterial infections.

Keywords

References

  1. Infect Immun. 2002 Mar;70(3):1075-80 [PMID: 11854185]
  2. Proc Natl Acad Sci U S A. 2019 Dec 16;: [PMID: 31843919]
  3. Biochemistry. 2002 Feb 19;41(7):2254-63 [PMID: 11841217]
  4. Biomaterials. 2014 Sep;35(27):8028-39 [PMID: 24952979]
  5. Sci Rep. 2018 Jul 11;8(1):10446 [PMID: 29993029]
  6. Amino Acids. 2017 Oct;49(10):1653-1677 [PMID: 28823054]
  7. Amino Acids. 2016 May;48(5):1241-51 [PMID: 26795535]
  8. Exp Lung Res. 2018 Aug;44(6):263-271 [PMID: 30595050]
  9. Biochim Biophys Acta Gen Subj. 2020 Apr;1864(4):129532 [PMID: 31953126]
  10. Infect Immun. 2014 Nov;82(11):4718-28 [PMID: 25156721]
  11. Peptides. 2019 Feb;112:56-66 [PMID: 30500360]
  12. Appl Microbiol Biotechnol. 2013 Feb;97(4):1711-23 [PMID: 22923068]
  13. Biomed Res Int. 2016;2016:2475067 [PMID: 27274985]
  14. Zool Res. 2019 Nov 18;40(6):488-505 [PMID: 31592585]
  15. Crit Rev Food Sci Nutr. 2017 Sep 2;57(13):2857-2876 [PMID: 26464037]
  16. Sci Rep. 2016 Aug 16;6:31492 [PMID: 27526963]
  17. Biochim Biophys Acta. 2006 Sep;1758(9):1513-22 [PMID: 16854372]
  18. Med Princ Pract. 2016;25(4):301-8 [PMID: 26684017]
  19. Expert Rev Mol Diagn. 2017 Mar;17(3):257-269 [PMID: 28093921]
  20. Adv Colloid Interface Sci. 2014 Mar;205:265-74 [PMID: 23910480]
  21. Biochim Biophys Acta. 2016 May;1858(5):926-35 [PMID: 26751595]
  22. J Antimicrob Chemother. 2009 Mar;63(3):534-42 [PMID: 19147523]
  23. Sci Transl Med. 2018 Jan 10;10(423): [PMID: 29321257]
  24. J Colloid Interface Sci. 2010 May 15;345(2):160-7 [PMID: 20185142]
  25. Bioconjug Chem. 2004 May-Jun;15(3):530-5 [PMID: 15149180]
  26. Chem Biol Drug Des. 2018 Aug;92(2):1504-1513 [PMID: 29682907]
  27. Int J Antimicrob Agents. 2007 Nov;30 Suppl 1:S71-5 [PMID: 17698326]
  28. Peptides. 2014 Dec;62:32-7 [PMID: 25285879]
  29. Antimicrob Resist Infect Control. 2019 Aug 13;8:137 [PMID: 31417673]
  30. Curr Top Med Chem. 2017;17(5):620-628 [PMID: 27411322]
  31. J Glob Health. 2016 Jun;6(1):010306 [PMID: 27350872]
  32. J Virol. 2015 Aug;89(15):7841-51 [PMID: 25995265]
  33. Amino Acids. 2016 Jan;48(1):203-11 [PMID: 26319645]
  34. PLoS One. 2014 Jan 21;9(1):e86364 [PMID: 24466055]
  35. Microb Pathog. 2019 Nov;136:103712 [PMID: 31491551]
  36. Biochimie. 2011 Jan;93(1):18-31 [PMID: 21056615]
  37. Molecules. 2015 Mar 24;20(4):5286-98 [PMID: 25812150]
  38. J Med Chem. 2015 Aug 27;58(16):6533-48 [PMID: 26214729]
  39. Appl Microbiol Biotechnol. 2019 Feb;103(4):1765-1775 [PMID: 30607494]
  40. Biochem J. 2005 Sep 15;390(Pt 3):695-702 [PMID: 15907192]
  41. Colloids Surf B Biointerfaces. 2020 Mar;187:110835 [PMID: 32033885]
  42. Chem Biol Drug Des. 2019 Sep;94(5):1986-1999 [PMID: 31437351]
  43. Nat Rev Drug Discov. 2013 Oct;12(10):791-808 [PMID: 24080700]
  44. ACS Nano. 2018 Jun 26;12(6):5284-5296 [PMID: 29856606]
  45. ACS Infect Dis. 2016 Jun 10;2(6):442-450 [PMID: 27331141]
  46. Biomed Res Int. 2013;2013:972028 [PMID: 23984424]
  47. Nature. 2017 Feb 28;543(7643):15 [PMID: 28252092]
  48. Adv Mater. 2019 Feb;31(7):e1806024 [PMID: 30589118]
  49. Eur J Med Chem. 2019 Nov 15;182:111636 [PMID: 31466017]
  50. J Med Chem. 2007 Jul 12;50(14):3334-9 [PMID: 17569519]
  51. GMS Infect Dis. 2018 Aug 09;6:Doc05 [PMID: 30671336]
  52. Int J Nanomedicine. 2017 Jun 30;12:4691-4708 [PMID: 28721045]
  53. Front Pharmacol. 2018 Nov 13;9:1297 [PMID: 30483133]
  54. Biochem J. 2004 Feb 15;378(Pt 1):93-103 [PMID: 14609430]
  55. Eur J Pharm Sci. 2020 Jan 1;141:105123 [PMID: 31676352]
  56. Clin Surg. 2017 Nov;2: [PMID: 30135956]
  57. Drugs. 2003;63(4):389-406 [PMID: 12558461]
  58. PLoS One. 2015 Dec 11;10(12):e0144611 [PMID: 26656394]

MeSH Term

Animals
Anti-Bacterial Agents
Anti-Infective Agents
Antimicrobial Cationic Peptides
Mice
Microbial Sensitivity Tests
Pore Forming Cytotoxic Proteins
Pseudomonas aeruginosa

Chemicals

Anti-Bacterial Agents
Anti-Infective Agents
Antimicrobial Cationic Peptides
Pore Forming Cytotoxic Proteins

Word Cloud

Created with Highcharts 10.0.0peptideMyr-36PWPMAP-36PWbacteriaAntimicrobialantimicrobialactivityantibacterialinfectionsdesignedN-terminalmyristoylationstabilityanti-biofilmbacterialtherapeuticDrug-resistantdrugresiduesincreasingcausingantibioticresistancepublichealththreatsworldwidepeptidesAMPsnoveldrugspotentialsolveproblemsbasedpreviouslystudiedviareferredfattyacidmodificationprovidedas-preparedgoodhighercomparedMoreoverexhibitedeffectiveGram-negativemaykillimprovingpermeabilitymembranesadditioninhibitgrowthATCC25923GIM1551targetorgansdecreaseinflammatorydamageshowimpressiveeffectmousepneumoniaperitonitisexperimentspromoteabscessreductionwoundhealinginfectedmiceresultsrevealpromisingagentMyristoylationEnhancedActivityPeptidemechanismefficacy

Similar Articles

Cited By