Modification and Synergistic Studies of a Novel Frog Antimicrobial Peptide against Biofilms.

Xinze Liu, Daning Shi, Shiya Cheng, Xiaoling Chen, Chengbang Ma, Yangyang Jiang, Tao Wang, Tianbao Chen, Chris Shaw, Lei Wang, Mei Zhou
Author Information
  1. Xinze Liu: Natural Drug Discovery Group, School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK.
  2. Daning Shi: Chinese Academy of Agricultural Sciences, No. 12 Zhongguancun South Street, Haidian District, Beijing 100081, China.
  3. Shiya Cheng: Natural Drug Discovery Group, School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK.
  4. Xiaoling Chen: Natural Drug Discovery Group, School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK.
  5. Chengbang Ma: Natural Drug Discovery Group, School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK.
  6. Yangyang Jiang: Natural Drug Discovery Group, School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK.
  7. Tao Wang: Natural Drug Discovery Group, School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK. ORCID
  8. Tianbao Chen: Natural Drug Discovery Group, School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK. ORCID
  9. Chris Shaw: Natural Drug Discovery Group, School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK.
  10. Lei Wang: Natural Drug Discovery Group, School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK. ORCID
  11. Mei Zhou: Natural Drug Discovery Group, School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK. ORCID

Abstract

The overuse of traditional antibiotics has resulted in bacterial resistance and seriously compromised the therapeutic efficacy of traditional antibiotics, making the exploration of new antimicrobials particularly important. Several studies have shown that bioactive peptides have become an important source of new antimicrobial drugs due to their broad-spectrum antibacterial action and lack of susceptibility to resistance. In this study, a novel bioactive peptide Nigrosin-6VL was characterised from the skin secretion of the golden cross band frog, , by using the 'shotgun' cloning strategy. Modifications on the Rana Box of Nigrosin-6VL revealed its critical role in antimicrobial functions. The peptide analogue, 2170-2R, designed to preserve the Rana Box structure while enhancing cationicity, exhibited improved therapeutic efficacy, particularly against Gram-negative bacteria, with a therapeutic value of 45.27. Synergistic studies demonstrated that 2170-2R inherits the synergistic antimicrobial activities of the parent peptides and effectively enhances the antimicrobial capacity of cefepime and gentamicin against both planktonic cells and biofilms. Specifically, 2170-2R can synergise effectively with cefepime and gentamicin against different strains of biofilms. Consequently, 2170-2R holds promise as a potent antimicrobial agent developed to combat infections induced by .

Keywords

References

  1. EMBO J. 1998 Nov 16;17(22):6437-48 [PMID: 9822590]
  2. Antibiotics (Basel). 2020 Feb 14;9(2): [PMID: 32075067]
  3. Int J Antimicrob Agents. 2009 Mar;33(3):201-5 [PMID: 18976888]
  4. J Proteome Res. 2012 Jan 1;11(1):306-19 [PMID: 22029824]
  5. J Pept Sci. 2014 Jul;20(7):453-67 [PMID: 24729276]
  6. Molecules. 2020 Jun 19;25(12): [PMID: 32575664]
  7. Clin Microbiol Rev. 2002 Apr;15(2):194-222 [PMID: 11932230]
  8. Front Microbiol. 2019 Aug 09;10:1703 [PMID: 31447797]
  9. J Infect Public Health. 2017 Jul - Aug;10(4):369-378 [PMID: 27616769]
  10. J Med Chem. 2017 Mar 23;60(6):2257-2270 [PMID: 28230992]
  11. J Genet Eng Biotechnol. 2022 May 23;20(1):76 [PMID: 35606468]
  12. Drug Des Devel Ther. 2017 Mar 22;11:939-946 [PMID: 28356719]
  13. Peptides. 2011 Apr;32(4):670-6 [PMID: 21193000]
  14. Biotechnol Adv. 2011 Jan-Feb;29(1):67-74 [PMID: 20817088]
  15. Sci Rep. 2015 Nov 04;5:15963 [PMID: 26530005]
  16. J Infect Dis. 1974 Apr;129(4):391-401 [PMID: 4361582]
  17. Biochem Pharmacol. 2017 Jun 1;133:43-62 [PMID: 27765485]
  18. Trends Microbiol. 2011 Aug;19(8):419-26 [PMID: 21664819]
  19. Microbes Infect. 2003 Nov;5(13):1213-9 [PMID: 14623017]
  20. Curr Opin Pharmacol. 2006 Oct;6(5):468-72 [PMID: 16890021]
  21. Peptides. 2014 Dec;62:32-7 [PMID: 25285879]
  22. J Bacteriol. 2010 Dec;192(23):6191-9 [PMID: 20935098]
  23. Materials (Basel). 2018 Dec 05;11(12): [PMID: 30563067]
  24. Chembiochem. 2008 Sep 1;9(13):2081-6 [PMID: 18677735]
  25. Biophys J. 2022 Nov 15;121(22):4368-4381 [PMID: 36199252]
  26. Toxins (Basel). 2021 Aug 31;13(9): [PMID: 34564615]
  27. Biotechnol Adv. 2019 Jan - Feb;37(1):177-192 [PMID: 30500353]
  28. Curr Opin Pharmacol. 2009 Oct;9(5):558-65 [PMID: 19748829]
  29. Biochimie. 2010 Sep;92(9):1236-41 [PMID: 20188791]
  30. Nat Prod Res. 2020 Mar;34(6):754-758 [PMID: 30470149]
  31. Molecules. 2020 Aug 24;25(17): [PMID: 32847059]
  32. Drug Resist Updat. 2000 Aug;3(4):247-255 [PMID: 11498392]
  33. Mol Cell Proteomics. 2007 May;6(5):882-94 [PMID: 17272268]
  34. Curr Opin Pulm Med. 2009 Mar;15(2):138-42 [PMID: 19532029]
  35. Curr Top Microbiol Immunol. 2016;398:147-183 [PMID: 26942418]
  36. Nat Rev Microbiol. 2005 Mar;3(3):238-50 [PMID: 15703760]
  37. Nat Rev Drug Discov. 2020 May;19(5):311-332 [PMID: 32107480]
  38. Chem Rev. 2015 Feb 25;115(4):1760-846 [PMID: 25594509]
  39. Microbiol Rev. 1996 Sep;60(3):539-74 [PMID: 8840786]
  40. J Biotechnol. 2014 Dec 10;191:121-30 [PMID: 25240440]
  41. Front Cell Infect Microbiol. 2017 Feb 15;7:39 [PMID: 28261568]
  42. Front Microbiol. 2018 Nov 28;9:2846 [PMID: 30555431]
  43. Front Med (Lausanne). 2017 Oct 30;4:183 [PMID: 29164118]
  44. Nat Rev Microbiol. 2011 Dec 28;10(2):123-36 [PMID: 22203377]
  45. Molecules. 2016 Sep 12;21(9): [PMID: 27626405]
  46. Biosci Rep. 2018 Jun 21;38(3): [PMID: 29752337]
  47. Clin Microbiol Infect. 2017 Jul;23(7):454-459 [PMID: 28111294]
  48. FEBS Lett. 2001 Oct 19;507(1):95-100 [PMID: 11682065]
  49. J Pept Sci. 2017 Apr;23(4):329-333 [PMID: 28176481]
  50. Biopolymers. 2003;71(1):28-48 [PMID: 12712499]
  51. Protein Sci. 2020 Mar;29(3):654-669 [PMID: 31899563]
  52. ACS Appl Mater Interfaces. 2021 Apr 14;13(14):16062-16074 [PMID: 33797891]
  53. Colloids Surf B Biointerfaces. 2021 Jun;202:111682 [PMID: 33714188]
  54. Peptides. 2006 Sep;27(9):2111-7 [PMID: 16621155]

Word Cloud

Created with Highcharts 10.0.0antimicrobial2170-2RantibioticstherapeuticpeptidespeptidetraditionalresistanceefficacynewparticularlyimportantstudiesbioactiveNigrosin-6VLRanaBoxSynergisticeffectivelycefepimegentamicinbiofilmsoveruseresultedbacterialseriouslycompromisedmakingexplorationantimicrobialsSeveralshownbecomesourcedrugsduebroad-spectrumantibacterialactionlacksusceptibilitystudynovelcharacterisedskinsecretiongoldencrossbandfrogusing'shotgun'cloningstrategyModificationsrevealedcriticalrolefunctionsanaloguedesignedpreservestructureenhancingcationicityexhibitedimprovedGram-negativebacteriavalue4527demonstratedinheritssynergisticactivitiesparentenhancescapacityplanktoniccellsSpecificallycansynergisedifferentstrainsConsequentlyholdspromisepotentagentdevelopedcombatinfectionsinducedModificationStudiesNovelFrogAntimicrobialPeptideBiofilmsPseudomonasaeruginosaAMPsco-administrationmodification

Similar Articles

Cited By