Octominin: A Novel Synthetic Anticandidal Peptide Derived from Defense Protein of Octopus Minor

Overview

Journal Mar Drugs

Publisher MDPI

Specialties Biology
Pharmacology

Date 2020 Jan 19

PMID 31952292

Citations 15

Authors

Chamilani Nikapitiya

S H S Dananjaya

H P S U Chandrarathna

Mahanama De Zoysa

Ilson Whang

Affiliations

Soon will be listed here.

Abstract

The rapid emergence of multidrug-resistant pathogens makes an urgent need for discovering novel antimicrobial agents as alternatives to conventional antibiotics. Towards this end, we designed and synthesized a synthetic peptide of 23 amino acids (AAs) (GWLIRGAIHAGKAIHGLIHRRRH) from a defense protein 3 cDNA sequence of Octopus minor. The sequence of the peptide, which was named Octominin, had characteristic features of known antimicrobial peptides (AMPs) such as a positive charge (+5), high hydrophobic residue ratio (43%), and 1.86 kcal/mol of Boman index. Octominin was predicted to have an alpha-helix secondary structure. The synthesized Octominin was 2625.2 Da with 92.5% purity. The peptide showed a minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of 50 and 200 μg/mL, respectively, against Candida albicans. Field emission scanning electron microscopy observation confirmed that Octominin caused ultrastructural cell wall deformities in . In addition, propidium iodide penetrated the Octominin-treated cells, further demonstrating loss of cell membrane integrity that caused cell death at both MIC and MFC. Octominin treatment increased the production of intracellular reactive oxygen species and decreased cell viability in a concentration dependent manner. Cytotoxicity assays revealed no significant influence of Octominin on the viability of human embryonic kidney 293T cell line, with over 95% live cells in the Octominin-treated group observed up to 100 µg/mL. Moreover, we confirmed the antifungal action of Octominin using a zebrafish experimental infection model. Overall, our results demonstrate the Octominin is a lead compound for further studies, which exerts its effects by inducing cell wall damage, causing loss of cell membrane integrity, and elevating oxidative stress.

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References

Silphaduang U, Noga E . Peptide antibiotics in mast cells of fish. Nature. 2001; 414(6861):268-9. DOI: 10.1038/35104690. View

Chia T, Wu Y, Chen J, Chi S . Antimicrobial peptides (AMP) with antiviral activity against fish nodavirus. Fish Shellfish Immunol. 2009; 28(3):434-9. DOI: 10.1016/j.fsi.2009.11.020. View

Veerman E, Nazmi K, Vant Hof W, Bolscher J, den Hertog A, Nieuw Amerongen A . Reactive oxygen species play no role in the candidacidal activity of the salivary antimicrobial peptide histatin 5. Biochem J. 2004; 381(Pt 2):447-52. PMC: 1133851. DOI: 10.1042/BJ20040208. View

Gallo R, Ono M, Povsic T, Page C, Eriksson E, Klagsbrun M . Syndecans, cell surface heparan sulfate proteoglycans, are induced by a proline-rich antimicrobial peptide from wounds. Proc Natl Acad Sci U S A. 1994; 91(23):11035-9. PMC: 45161. DOI: 10.1073/pnas.91.23.11035. View

Park Y, Jang S, Lee D, Hahm K . Antinematodal effect of antimicrobial peptide, PMAP-23, isolated from porcine myeloid against Caenorhabditis elegans. J Pept Sci. 2004; 10(5):304-11. DOI: 10.1002/psc.518. View

Ye X, Ng T . Isolation of a new cyclophilin-like protein from chickpeas with mitogenic, antifungal and anti-HIV-1 reverse transcriptase activities. Life Sci. 2002; 70(10):1129-38. DOI: 10.1016/s0024-3205(01)01473-4. View

Bellamy W, Wakabayashi H, Takase M, Kawase K, Shimamura S, Tomita M . Killing of Candida albicans by lactoferricin B, a potent antimicrobial peptide derived from the N-terminal region of bovine lactoferrin. Med Microbiol Immunol. 1993; 182(2):97-105. DOI: 10.1007/BF00189377. View

Samaranayake Y, Cheung B, Wang Y, Yau J, Yeung K, Samaranayake L . Fluconazole resistance in Candida glabrata is associated with increased bud formation and metallothionein production. J Med Microbiol. 2012; 62(Pt 2):303-318. DOI: 10.1099/jmm.0.044123-0. View

Manohar V, Ingram C, Gray J, Talpur N, Echard B, Bagchi D . Antifungal activities of origanum oil against Candida albicans. Mol Cell Biochem. 2002; 228(1-2):111-7. DOI: 10.1023/a:1013311632207. View

10.

Lee D, Kim D, Park Y, Kim H, Kim H, Shin Y . Fungicidal effect of antimicrobial peptide, PMAP-23, isolated from porcine myeloid against Candida albicans. Biochem Biophys Res Commun. 2001; 282(2):570-4. DOI: 10.1006/bbrc.2001.4602. View

11.

Lee D, Park Y, Kim H, Kim H, Kim P, Choi B . Antifungal mechanism of an antimicrobial peptide, HP (2--20), derived from N-terminus of Helicobacter pylori ribosomal protein L1 against Candida albicans. Biochem Biophys Res Commun. 2002; 291(4):1006-13. DOI: 10.1006/bbrc.2002.6548. View

12.

Park S, Kim J, Jeong C, Yoo S, Hahm K, Park Y . A plausible mode of action of pseudin-2, an antimicrobial peptide from Pseudis paradoxa. Biochim Biophys Acta. 2010; 1808(1):171-82. DOI: 10.1016/j.bbamem.2010.08.023. View

13.

Lai Y, Gallo R . AMPed up immunity: how antimicrobial peptides have multiple roles in immune defense. Trends Immunol. 2009; 30(3):131-41. PMC: 2765035. DOI: 10.1016/j.it.2008.12.003. View

14.

Scott M, Yan H, Hancock R . Biological properties of structurally related alpha-helical cationic antimicrobial peptides. Infect Immun. 1999; 67(4):2005-9. PMC: 96559. DOI: 10.1128/IAI.67.4.2005-2009.1999. View

15.

de Alteriis E, Maselli V, Falanga A, Galdiero S, Di Lella F, Gesuele R . Efficiency of gold nanoparticles coated with the antimicrobial peptide indolicidin against biofilm formation and development of spp. clinical isolates. Infect Drug Resist. 2018; 11:915-925. PMC: 6037145. DOI: 10.2147/IDR.S164262. View

16.

Wang Z, Wang G . APD: the Antimicrobial Peptide Database. Nucleic Acids Res. 2003; 32(Database issue):D590-2. PMC: 308759. DOI: 10.1093/nar/gkh025. View

17.

Kavanagh K, Dowd S . Histatins: antimicrobial peptides with therapeutic potential. J Pharm Pharmacol. 2004; 56(3):285-9. DOI: 10.1211/0022357022971. View

18.

Peixoto L, Rosalen P, Ferreira G, Freires I, de Carvalho F, Castellano L . Antifungal activity, mode of action and anti-biofilm effects of Laurus nobilis Linnaeus essential oil against Candida spp. Arch Oral Biol. 2016; 73:179-185. DOI: 10.1016/j.archoralbio.2016.10.013. View

19.

De Zoysa M, Nikapitiya C, Whang I, Lee J, Lee J . Abhisin: a potential antimicrobial peptide derived from histone H2A of disk abalone (Haliotis discus discus). Fish Shellfish Immunol. 2009; 27(5):639-46. DOI: 10.1016/j.fsi.2009.08.007. View

20.

Maurya I, Pathak S, Sharma M, Sanwal H, Chaudhary P, Tupe S . Antifungal activity of novel synthetic peptides by accumulation of reactive oxygen species (ROS) and disruption of cell wall against Candida albicans. Peptides. 2011; 32(8):1732-40. DOI: 10.1016/j.peptides.2011.06.003. View