Skip to main content
SpringerLink
Log in

A histone H2A-derived antimicrobial peptide, Hipposin from mangrove whip ray, Himantura walga: Molecular and functional characterisation

  • Original Article
  • Published:
3 Biotech Aims and scope Submit manuscript

Abstract

Antimicrobial peptides (AMPs) are biologically dynamic molecules produced by all type of organisms as a fundamental component of their innate immune system. The present study deals with the identification of a histone H2A-derived antimicrobial peptide, Hipposin from mangrove whip ray, Himantura walga. A 243 base pair fragment encoding 81 amino acid residues amplified from complementary DNA was identified as Hipposin and termed as Hw-Hip. Homologous analysis showed that Hw-Hip belongs to the Histone H2A superfamily and shares sequence identity with other histone-derived AMPs from fishes. Phylogenetic analysis of Hw-Hip displayed clustering with the fish H2A histones. Secondary structure analysis showed the presence of three α-helices and four random coils with a prominent proline hinge. The physicochemical properties of Hw-Hip are in agreement with the properties of antimicrobial peptides. A 39-mer active peptide sequence was released by proteolytic cleavage in silico. Functional characterisation of active peptide in silico revealed antibacterial, anticancer and antibiofilm activities making Hw-Hip a promising candidate for further exploration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  • Ansari JM, Abraham NM, Massaro J, Murphy K, Smith-Carpenter J, Fikrig E (2017) Anti-biofilm activity of a self-aggregating peptide against Streptococcus mutans. Front Microbiol 8:488

    PubMed  PubMed Central  Google Scholar 

  • Arockiaraj J, Gnanam AJ, Kumaresan V, Palanisamy R, Bhatt P, Thirumalai MK, Kasi M (2013) An unconventional antimicrobial protein histone from freshwater prawn Macrobrachium rosenbergii: analysis of immune properties. Fish shellfish immun 35:1511–1522

    CAS  Google Scholar 

  • Birkemo GA, Lüders T, Andersen Ø, Nes IF, Nissen-Meyer J (2003) Hipposin, a histone-derived antimicrobial peptide in Atlantic halibut (Hippoglossus hippoglossus L.). Biochim Biophys Acta 1646:207–215

    CAS  PubMed  Google Scholar 

  • Boman HG (2003) Antibacterial peptides: basic facts and emerging concepts. J Intern Med 254:197–215

    CAS  PubMed  Google Scholar 

  • Caccia E, Agnello M, Ceci M, Strickler Dinglasan P, Vasta GR, Romano N (2017) Antimicrobial peptides are expressed during early development of zebrafish (Danio rerio) and are inducible by immune challenge. Fishes 2:20

    Google Scholar 

  • Chaithanya ER, Philip R, Sathyan N, Anil Kumar PR (2013) Molecular characterization and phylogenetic analysis of a histone-derived antimicrobial peptide teleostin from the marine teleost fishes. Tachysurus jella and Cynoglossus semifasciatus. ISRN Mol, Biol

  • Chen B, Fan DQ, Zhu KX, Shan ZG, Chen FY, Hou L, Wang KJ (2015) Mechanism study on a new antimicrobial peptide Sphistin derived from the N-terminus of crab histone H2A identified in haemolymphs of Scylla paramamosain. Fish shellfish Immun 47:833–846

    CAS  Google Scholar 

  • Cho JH, Park IY, Kim HS, Lee WT, Kim MS, Kim SC (2002) Cathepsin D produces antimicrobial peptide parasin I from histone H2A in the skin mucosa of fish. FASEB J 16:429–431

    CAS  PubMed  Google Scholar 

  • Cho JH, Sung BH, Kim SC (2009) Buforins: histone H2A-derived antimicrobial peptides from toad stomach. BBA-Biomembranes 1788:1564–1569

    CAS  PubMed  Google Scholar 

  • Cutrona KJ, Kaufman BA, Figueroa DM, Elmore DE (2015) Role of arginine and lysine in the antimicrobial mechanism of histone-derived antimicrobial peptides. FEBS Lett 589:3915–3920

    CAS  PubMed  PubMed Central  Google Scholar 

  • De Zoysa M, Nikapitiya C, Whang I, Lee JS, Lee J (2009) Abhisin: a potential antimicrobial peptide derived from histone H2A of disk abalone (Haliotis discus discus). Fish shellfish Immun 27:639–646

    Google Scholar 

  • DeLano WL (2002) Pymol: an open-source molecular graphics tool. CCP4 Newsletter Protein Crystallogr 40:82–92

    Google Scholar 

  • Deng B, Luo Q, Halim A, Liu Q, Zhang B, Song G (2020) The antiangiogenesis role of histone deacetylase inhibitors: their potential application to tumour therapy and tissue repair. DNA Cell Biol 39:167–176

    CAS  PubMed  Google Scholar 

  • Fernandes JM, Kemp GD, Molle MG, Smith VJ (2002) Anti-microbial properties of histone H2A from skin secretions of rainbow trout, Oncorhynchus mykiss. Biochem J 368:611–620

    CAS  PubMed  PubMed Central  Google Scholar 

  • Habets MG, Brockhurst MA (2012) Therapeutic antimicrobial peptides may compromise natural immunity. Biol Lett 8:416–418

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hill CS, Rimmer JM, Green BN, Finch JT, Thomas JO (1991) Histone-DNA interactions and their modulation by phosphorylation of-Ser-Pro-X-Lys/Arg-motifs. EMBO J 10:1939–1948

    CAS  PubMed  PubMed Central  Google Scholar 

  • Izadpanah A, Gallo RL (2005) Antimicrobial peptides. J Am Acad Dermatol 52:381–390

    PubMed  Google Scholar 

  • Jodoin J, Hincke MT (2018) Histone H5 is a potent antimicrobial agent and a template for novel antimicrobial peptides. Sci Rep 8:1–15

    CAS  Google Scholar 

  • Katzenback BA (2015) Antimicrobial peptides as mediators of innate immunity in teleosts. Biology 4:607–639

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kawasaki H, Iwamuro S (2008) Potential roles of histones in host defense as antimicrobial agents. Infect Disord Drug Targets 8:195–205

    CAS  PubMed  Google Scholar 

  • Kawasaki H, Koyama T, Conlon JM, Yamakura F, Iwamuro S (2008) Antimicrobial action of histone H2B in Escherichia coli: evidence for membrane translocation and DNA-binding of a histone H2B fragment after proteolytic cleavage by outer membrane proteinase. T Biochim 90:1693–1702

    CAS  Google Scholar 

  • Kim HS, Park CB, Kim MS, Kim SC (1996) cDNA cloning and characterization of buforin I, an antimicrobial peptide: a cleavage product of histone H2A. Biochem Biophys Res Commun 229:381–387

    CAS  PubMed  Google Scholar 

  • Kim HS, Yoon H, Minn I, Park CB, Lee WT, Zasloff M, Kim SC (2000) Pepsin-mediated processing of the cytoplasmic histone H2A to strong antimicrobial peptide buforin I. J Immunol 165:3268–3274

    CAS  PubMed  Google Scholar 

  • Kobayashi S, Takeshima K, Park CB, Kim SC, Matsuzaki K (2000) Interactions of the novel antimicrobial peptide buforinII with lipid bilayers: proline as a translocation promoting factor. Biochemistry US 39:8648–8654

    CAS  Google Scholar 

  • Koo YS, Kim JM, Park IY, Yu BJ, Jang SA, Kim KS, Kim SC (2008) Structure–activity relations of parasin I, a histone H2A-derived antimicrobial peptide. Peptides 29:1102–1108

    CAS  PubMed  Google Scholar 

  • Lee HS, Park CB, Kim JM, Jang SA, Park IY, Kim MS, Kim SC (2008) Mechanism of anticancer activity of buforin IIb, a histone H2A-derived peptide. Cancer Lett 271:47–55

    CAS  PubMed  Google Scholar 

  • Lewies A, Du Plessis LH, Wentzel JF (2019) Antimicrobial peptides: the Achilles heel of antibiotic resistance. Probiot Antimicrob Proteins 11:370–381

    CAS  Google Scholar 

  • Li C, Song L, Zhao J, Zhu L, Zou H, Zhang H, Cai Z (2007) Preliminary study on a potential antibacterial peptide derived from histone H2A in hemocytes of scallop Chlamys farreri. Fish shellfish Immun 22:663–672

    Google Scholar 

  • McDougall SR, Anderson AR, Chaplain MA (2006) Mathematical modelling of dynamic adaptive tumour-induced angiogenesis: clinical implications and therapeutic targeting strategies.J. Theor Biol 241:564–589

    Google Scholar 

  • Morin V, Acuña P, Díaz F, Inostroza D, Martinez J, Montecino M, Imschenetzky M (2000) Phosphorylation protects sperm-specific histones H1 and H2B from proteolysis after fertilization. J Cell Biochem 76:173–180

    CAS  Google Scholar 

  • Okuda KI, Zendo T, Sugimoto S, Iwase T, Tajima A, Yamada S, Mizunoe Y (2013) Effects of bacteriocins on methicillin-resistant Staphylococcus aureus biofilm. Antimicrob Agents Chemother 57:5572–5579

    CAS  PubMed  PubMed Central  Google Scholar 

  • Papo N, Shai Y (2005) Host defense peptides as new weapons in cancer treatment. Cell Mol Life Sci 62:784–790

    CAS  PubMed  Google Scholar 

  • Park CB, Kim MS, Kim SC (1996) A novel antimicrobial peptide from Bufo bufo gargarizans. Biochem Biophys Res Commun 218:408–413

    CAS  PubMed  Google Scholar 

  • Park IY, Park CB, Kim MS, Kim SC (1998) Parasin I, an antimicrobial peptide derived from histone H2A in the catfish, Parasilurus asotus. FEBS Lett 437:258–262

    CAS  PubMed  Google Scholar 

  • Park CB, Yi KS, Matsuzaki K, Kim MS, Kim SC (2000) Structure–activity analysis of buforin II, a histone H2A-derived antimicrobial peptide: the proline hinge is responsible for the cell-penetrating ability of buforin II. Proc Natl Acad Sci USA 97:8245–8250

    CAS  PubMed  Google Scholar 

  • Parseghian MH, Luhrs KA (2006) Beyond the walls of the nucleus: the role of histones in cellular signalling and innate immunity. Biochem Cell Biol 84:589–595

    CAS  PubMed  Google Scholar 

  • Patat SA, Carnegie RB, Kingsbury C, Gross PS, Chapman R, Schey KL (2004) Antimicrobial activity of histones from hemocytes of the Pacific white shrimp. Eur J Biochem 271:4825–4833

    CAS  PubMed  Google Scholar 

  • Pavia KE, Spinella SA, Elmore DE (2012) Novel histone-derived antimicrobial peptides use different antimicrobial mechanisms. BBA-Biomembranes 1818:869–876

    CAS  PubMed  Google Scholar 

  • Pletzer D, Coleman SR, Hancock RE (2016) Anti-biofilm peptides as a new weapon in antimicrobial warfare. Curr Opin Microbiol 33:35–40

    CAS  PubMed  PubMed Central  Google Scholar 

  • Poirier AC, Schmitt P, Rosa RD, Vanhove AS, Kieffer-Jaquinod S, Rubio TP, Destoumieux-Garzón D (2014) Antimicrobial Histones and DNA Traps in Invertebrate Immunity evidences in Crassostrea gigas. J Biol 289:24821–24831

    CAS  Google Scholar 

  • Richards RC, O’Neil DB, Thibault P, Ewart KV (2001) Histone H1: an antimicrobial protein of Atlantic salmon (Salmo salar). Biochem Biophys Res Commun 284:549–555

    CAS  PubMed  Google Scholar 

  • Rohde H, Frankenberger S, Zähringer U, Mack D (2010) Structure, function and contribution of polysaccharide intercellular adhesin (PIA) to Staphylococcus epidermidis biofilm formation and pathogenesis of biomaterial-associated infections. Eur J Cell Biol 89:103–111

    CAS  PubMed  Google Scholar 

  • Rose-Martel M, Hincke MT (2014) Antimicrobial histones from chicken erythrocytes bind bacterial cell wall lipopolysaccharides and lipoteichoic acids. Int J Antimicrob Agents 44:470–472

    CAS  PubMed  Google Scholar 

  • Rose-Martel M, Kulshreshtha G, Berhane NA, Jodoin J, Hincke MT (2017) Histones from avian erythrocytes exhibit antibiofilm activity against methicillin-sensitive and methicillin-resistant Staphylococcus aureus. Sci Rep 7:45980

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sathyan N, Philip R, Chaithanya ER, Anil Kumar PR (2012a) Identification and molecular characterization of molluskin, a histone-H2A-derived antimicrobial peptide from molluscs. ISRN Mol Biol 2012:219656

    PubMed  PubMed Central  Google Scholar 

  • Sathyan N, Philip R, Chaithanya ER, Kumar PA, Antony SP (2012b) Identification of a histone derived, putative antimicrobial peptide Himanturin from round whip ray Himantura pastinacoides and its phylogenetic significance. Results Immunol 2:20–124

    Google Scholar 

  • Sathyan N, Philip R, Chaithanya ER, AnilKumar PR, Sanjeevan VN, Singh IS (2013) Characterization of Histone H2A derived antimicrobial peptides, Harriottins, from Sicklefin Chimaera Neoharriotta pinnata (Schnakenbeck, 1931) and its evolutionary divergence with respect to CO1 and Histone H2A. ISRN Mol Biol. https://doi.org/10.1155/2013/930216

    Article  PubMed  PubMed Central  Google Scholar 

  • Sharma A, Gupta P, Kumar R, Bhardwaj A (2016) dPABBs: a novel in silico approach for predicting and designing anti-biofilm peptides. Sci Rep 6:21839

    CAS  PubMed  PubMed Central  Google Scholar 

  • Spill F, Guerrero P, Alarcón T, Maini PK, Byrne HM (2015) Mesoscopic and continuum modelling of angiogenesis. J Math Biol 70:485–532

    CAS  PubMed  Google Scholar 

  • Sruthy KS, Nair A, Antony SP, Puthumana J, Singh IB, Philip R (2019) A histone H2A derived antimicrobial peptide, Fi-Histin from the Indian White shrimp, Fenneropenaeus indicus: molecular and functional characterization. Fish Shellfish Immun 92:667–679

    CAS  Google Scholar 

  • Tagai C, Morita S, Shiraishi T, Miyaji K, Iwamuro S (2011) Antimicrobial properties of arginine-and lysine-rich histones and involvement of bacterial outer membrane protease T in their differential mode of actions. Peptides 32:2003–2009

    CAS  PubMed  Google Scholar 

  • Tsao HS, Spinella SA, Lee AT, Elmore DE (2009) Design of novel histone-derived antimicrobial peptides. Peptides 30:2168–2173

    CAS  PubMed  Google Scholar 

  • Yi GS, Park CB, Kim SC, Cheong C (1996) Solution structure of an antimicrobial peptide buforin II. FEBS Lett 398:87–90

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors are grateful to the Director, Centre for Marine Living Resources and Ecology (CMLRE) and Ministry of Earth Sciences (MoES), Govt. of India for the research grant (MoES/10-MLR/01/2012) and scientific support for the work. The authors also thank Cochin University of Science and Technology for providing necessary facilities to carry out this work. The first author gratefully acknowledges CSIR (Council of Scientific & Industrial Research) for the award of a fellowship.

Author information

Authors and Affiliations

  1. Department of Marine Biology, Microbiology and Biochemistry, School of Marine Sciences, Cochin University of Science and Technology, Fine Arts Avenue, Kochi, Kerala, 682016, India

    P. P. Athira, M. V. Anju, V. V. Anooja, K. Archana, S. Neelima & Philip Rosamma

Authors
  1. P. P. Athira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. V. Anju
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V. V. Anooja
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K. Archana
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. Neelima
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Philip Rosamma
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Athira P P carried out the experiment with the support from Anju M V, Anooja V V, Archana K and Neelima S. Athira P P wrote the manuscript. Rosamma Philip supervised the work and corrected the manuscript.

Corresponding author

Correspondence to Philip Rosamma.

Ethics declarations

Conflict of interest

Authors declare that there is no conflict of interest.

Research involving human and animal participants

This article does not contain any study that requires ethical approval.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (JPEG 1401 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Athira, P.P., Anju, M.V., Anooja, V.V. et al. A histone H2A-derived antimicrobial peptide, Hipposin from mangrove whip ray, Himantura walga: Molecular and functional characterisation. 3 Biotech 10, 467 (2020). https://doi.org/10.1007/s13205-020-02455-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s13205-020-02455-3

Keywords

Search

Navigation