Skip to main content

Advertisement

Log in

Dicentracin-Like from Asian sea bass Fish and Moronecidine-Like from Hippocampus Comes: Two Candidate Antimicrobial Peptides Against Leishmanina major Infection

  • Published:
International Journal of Peptide Research and Therapeutics Aims and scope Submit manuscript

Abstract

Anti-Leishmanial drug therapy faces significant challenges related to cytotoxicity and drug resistance. Thus, new and efficient anti-Leishmanial drugs need to be identified. Due to their broad-spectrum antimicrobial and also immunomodulatory activities, antimicrobial peptides (AMPs) have attracted considerable attention. In this study, we comparatively assessed the anti-Leishmanial activities of two recently identified AMPs (dicentracin-like and moronecidine-like) and the well-known AMP piscidin from the hybrid striped bass. AMPs were first assessed against Leishmania major promastigotes using MTS. Subsequently, macrophages were infected with L. major and treated with AMPs to evaluate anti-amastigotes activity of AMPs, and non-infected macrophages were treated with AMPs to determine cytotoxicity against mammalian cells using MTS. The induction of factors limiting L. major growth (IL-12, TNF-α and reactive oxygen species (ROS)) by AMPs was measured by ELISA and dichlorofluorescin-diacetate (DCFH-DA) assay, respectively. Piscidin was more efficacious against L. major promastigotes as compared to dicentracine-like or moronocidin-like peptides, whereas, dicentracine-like and moronocidin-like peptide exhibited a higher activity against L. major amastigotes compared to piscidin. In turn, piscidin was most cytotoxic in non-infected macrophages compared to the other two AMPs. A direct association was observed between hydrophobicity of AMPs and their anti-promastigote and cytotoxic activities. Dicentracine-like or moronocidin-like peptides induced higher levels of IL-12, TNF-α and ROS in macrophages compared to piscidin. Collectively, our results suggest that dicentracine-like and moronocidin-like peptides represent potentially promising multi-functional therapeutic agents that might not only directly kill L. major but also induce anti-Leishmania factors that can limit L. major growth and intracellular survival.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Availability of Data and Material

The authors confirm that the data supporting the findings of this study are available within the manuscript.

References

  • Agier J, Efenberger M, Brzezińska-Błaszczyk E (2015) Cathelicidin impact on inflammatory cells. Cent Eur J Immunol 40:225–235

    Article  PubMed  PubMed Central  Google Scholar 

  • Ansari MY, Equbal A, Dikhit MR, Mansuri R, Rana S, Ali V, Sahoo GC, Das P (2016) Establishment of correlation between in-silico and in-vitro test analysis against Leishmania HGPRT to inhibitors. Int J Biol Macromol 83:78–96

    Article  CAS  PubMed  Google Scholar 

  • Chessa C, Bodet C, Jousselin C, Wehbe M, Lévêque N, Garcia M (2020) Antiviral and Immunomodulatory Properties of Antimicrobial Peptides Produced by Human Keratinocytes. Front Microbiol 11:1155. DOI https://doi.org/10.3389/fmicb.2020.01155

    Article  PubMed  PubMed Central  Google Scholar 

  • Chifiriuc MC, Grumezescu AM, Lazar V, Bolocan A, Triaridis S, Grigore R, Bertesteanu S (2014) Contribution of Antimicrobial Peptides to the Development of New and Efficient Antimicrobial Strategies. Curr Proteomics 11:98–107

    Article  CAS  Google Scholar 

  • Chiou PP, Lin CM, Perez L, Chen TT (2002) Effect of cecropin B and a synthetic analogue on propagation of fish viruses in vitro. Mar Biotechnol 4:294–302

    Article  CAS  Google Scholar 

  • Chiou TT, Wu JL, Chen TT, Lu JK (2005) Molecular cloning and characterization of cDNA of penaeidin-like antimicrobial peptide from tiger shrimp (Penaeus monodon). Mar Biotechnol 7:119–127

    Article  CAS  Google Scholar 

  • Cobb SL, Denny PW (2010) Antimicrobial peptides for leishmaniasis. Curr Opin Investig Drugs 11:868–875

    CAS  PubMed  Google Scholar 

  • Dayakar A, Chandrasekaran S, Kuchipudi SV. Kalangi SK (2019) Cytokines: key determinants of resistance or disease progression in visceral leishmaniasis: opportunities for novel diagnostics and immunotherapy. Front Immunol 10:670

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Diamond G, Beckloff N, Weinberg A, Kisich KO (2009) The roles of antimicrobial peptides in innate host defense. Curr Pharm Des 15:2377–2392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fan C, Wu LH, Zhang GF, Xu F, Zhang S, Zhang X, Sun L, Yu Y, Zhang Y (2017) 4’ Hydroxywogonin suppresses lipopolysaccharide-induced inflammatory responses in RAW 264.7 macrophages and acute lung injury mice. PLoS One. https://doi.org/10.1371/journal.pone.0181191

    Article  PubMed  PubMed Central  Google Scholar 

  • Fuertes MA, Nguewa PA, Castilla J, Alonso C, Pérez JM (2008) Anticancer compounds as leishmanicidal drugs: challenges in chemotherapy and future perspectives. Curr Med Chem 15:433–439

    Article  CAS  PubMed  Google Scholar 

  • Gharavi MJ, Nobakht M, Khademvatan SH, Fani F, Bakhshayesh M, Roozbehani M (2011a) The Effect of Aqueous Garlic Extract on Interleukin-12 and 10 Levels in Leishmania major (MRHO/IR/75/ER) Infected Macrophages. Iranian J Publ Health 40:105–111

    Google Scholar 

  • Guilhelmelli F, Vilela N, Albuquerque P, Derengowski Lda S, Silva-Pereira I, Kyaw CM (2013) Antibiotic development challenges: the various mechanisms of action of antimicrobial peptides and of bacterial resistance. Front Microbiol 4:353–365

    Article  PubMed  PubMed Central  Google Scholar 

  • Irazazabal LN, Porto WF, Ribeiro SM, Casale S, Humblot V, Ladram A, Franco OL (2016) Selective amino acid substitution reduces cytotoxicity of the antimicrobial peptide mastoparan. Biochim Biophys Acta 1858:2699–2708

    Article  CAS  PubMed  Google Scholar 

  • Kim JK, Lee SA, Shin S, Lee JY, Jeong KW, Nan YH, Park YS, Shin SY, Kim Y (2010) Structural flexibility and the positive charges are the key factors in bacterial cell selectivity and membrane penetration of peptoid-substituted analog of Piscidin 1. Biochim Biophys Acta 1798:1913–1925

    Article  CAS  PubMed  Google Scholar 

  • Kumar A, Tripathi AK, Kathuria M, Shree S, Tripathi JK, Purshottam RK, Ramachandran R, Mitra K, Ghosh JK (2016) Single Amino Acid Substitutions at Specific Positions of the Heptad Repeat Sequence of Piscidin-1 Yielded Novel Analogs That Show Low Cytotoxicity and In Vitro and In Vivo Antiendotoxin Activity. Antimicrob Agents Chemother 60:3687–3699

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lei J, Sun L, Huang S, Zhu C, Li P, He J, Mackey V, Coy DH, He Q (2019) The antimicrobial peptides and their potential clinical applications. Am J Transl Res 11:3919–3931

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lynn MA, Kindrachuk J, Marr AK, Jenssen H, Panté N, Elliott MR, Napper S, Hancock RE, McMaster WR (2011) Effect of BMAP-28 antimicrobial peptides on Leishmania major promastigote and amastigote growth: role of leishmanolysin in parasite survival. PLoS Negl Trop Dis. https://doi.org/10.1371/journal.pntd.0001141

    Article  PubMed  PubMed Central  Google Scholar 

  • Marr AK, McGwire BS, McMaster WR (2012) Modes of action of Leishmanicidal antimicrobial peptides. Future Microbiol 7:1047–1059

    Article  CAS  PubMed  Google Scholar 

  • Mitra AK, Mawson AR (2017) Neglected tropical diseases: epidemiology and global burden. Trop Med Infect Dis. https://doi.org/10.3390/tropicalmed2030036

    Article  PubMed  PubMed Central  Google Scholar 

  • Mohammad H, Thangamani S, Seleem MN (2015) Antimicrobial peptides and peptidomimetics - potent therapeutic allies for staphylococcal infections. Curr Pharm Des 21:2073–2088

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mohammadi M, Taheri B, Momenzadeh N, Salarinia R, Nabipour I, Farshadzadeh Z, Bargahi A (2018) Identification and characterization of novel antimicrobial peptide from hippocampus comes by in silico and experimental studies. Mar Biotechnol 20:718–728

    Article  CAS  Google Scholar 

  • Mor A (2009) Multifunctional host defense peptides: antiparasitic activities. Febs j 276:6474–6482

    Article  CAS  PubMed  Google Scholar 

  • Nayak T, Mandal SM, Neog K, Ghosh AK (2018) Characterization of a Gloverin-Like Antimicrobial Peptide Isolated from Muga Silkworm, Antheraea assamensis. Int J Pept Res Ther 24::337–346. DOI https://doi.org/10.1007/s10989-017-9618-0

    Article  CAS  Google Scholar 

  • Ngamprasertchai T, Boonyasiri A, Charoenpong L, Nimitvilai S, Lorchirachoonkul N, Wattanamongkonsil L, Thamlikitkul V (2018) Effectiveness and safety of polymyxin B for the treatment of infections caused by extensively drug-resistant Gram-negative bacteria in Thailand. Infect Drug Resist 11:1219–1224

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gharavi MJ, Nobakht M, Khademvatan SH, Bandani E, Bakhshayesh M, Roozbehani M (2011b) The Effect of Garlic Extract on Expression of INFγ And Inos Genes in Macrophages Infected with Leishmania major. Iranian J Parasitol 6:74–81

    Google Scholar 

  • Ponte-Sucre A, Gamarro F, Dujardin JC, Barrett MP, López-Vélez R, García-Hernández R, Pountainn AW, Mwenechanya R, Papadopoulou B (2017) Drug resistance and treatment failure in leishmaniasis: A 21st century challenge. PLoS Negl Trop Dis. https://doi.org/10.1371/journal.pntd.0006052

    Article  PubMed  PubMed Central  Google Scholar 

  • Roma EH, Macedo JP, Goes GR, Gonçalves JL, Castro W, Cisalpino D, Vieira LQ (2016) Impact of reactive oxygen species (ROS) on the control of parasite loads and inflammation in Leishmania amazonensis infection. Parasit Vectors. https://doi.org/10.1186/s13071-016-1472-y

    Article  PubMed  PubMed Central  Google Scholar 

  • Sathyamoorthi A, Kumaresan V, Palanisamy R, Pasupuleti M, Arasu MV, Al-Dhabi NA, Marimuthu K, Amin SN, Arshad A, Yusoff FM (2019) Therapeutic cationic antimicrobial peptide (CAP) derived from fish aspartic proteinase Cathepsin D and its antimicrobial mechanism. Int J Pept Res Ther 25:93–105

    Article  CAS  Google Scholar 

  • Shafiee F, Minaiyan G, Moazen F, Jahanian-Najafabadi A (2017) Recombinant Production and Intein-Mediated Purification of an Antimicrobial Peptide, BR2. Int J Pept Res Ther 23::501–507. DOI https://doi.org/10.1007/s10989-017-9583-7

    Article  CAS  Google Scholar 

  • Sundar S, Chakravarty J (2015) An update on pharmacotherapy for leishmaniasis. Expert Opin Pharmacother 16:237–252

    Article  CAS  PubMed  Google Scholar 

  • Taheri B, Mohammadi M, Momenzadeh N, Farshadzadeh Z, Roozbehani M, Dehghani P, Hajian S, Darvishi S, Shamseddin J (2019) Substitution of lysine for isoleucine at the center of the nonpolar face of the antimicrobial peptide, piscidin-1, leads to an increase in the rapidity of bactericidal activity and a reduction in toxicity. Infect Drug Resist 12:1629–1647

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Taheri B, Mohammadi M, Nabipour I, Momenzadeh N, Roozbehani M (2018) Identification of novel antimicrobial peptide from Asian sea bass (Lates calcarifer) by in silico and activity characterization. PLoS One. https://doi.org/10.1371/journal.pone.0206578

    Article  PubMed  PubMed Central  Google Scholar 

  • Torrent M, Pulido D, Rivas L, Andreu D (2012) Antimicrobial peptide action on parasites. Curr Drug Targets 13:1138–1147

    Article  CAS  PubMed  Google Scholar 

  • Vaara M (2019) Polymyxin derivatives that sensitize Gram-Negative bacteria to other antibiotics. Molecules. https://doi.org/10.3390/molecules24020249

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang S, Ye Q, Wang K, Zeng X, Huang S, Yu H, Ge Q, Qi D, Qiao S (2019) Enhancement of macrophage function by the antimicrobial peptide sublancin protects mice from methicillin-resistant Staphylococcus aureus. J Immunol Res 2019:3979–352

    Google Scholar 

  • Wozencraft A, Blackwell J (1987) Increased infectivity of stationary-phase promastigotes of Leishmania donovani: correlation with enhanced C3 binding capacity and CR3-mediated attachment to host macrophages. Immunology 60:559

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang W, Li Z, Miao X, Zhang F (2009) The screening of antimicrobial bacteria with diverse novel nonribosomal peptide synthetase (NRPS) genes from South China sea sponges. Mar Biotechnol 11:346–355

    Article  Google Scholar 

  • Zheng Y, Niyonsaba F, Ushio H, Nagaoka I, Ikeda S, Okumura K, Ogawa H (2007) Cathelicidin LL-37 induces the generation of reactive oxygen species and release of human alpha-defensins from neutrophils. Br J Dermatol 157:1124–1131

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Bushehr University of Medical Sciences for providing research budget. This was supported by a research Grant (Code: 1218) from Bushehr University of Medical Sciences.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Moradali Fouladvand.

Ethics declarations

Conflict of interest

The authors declare that there are no conflicts of interest regarding the publication of this article.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Electronic supplementary material 1 (PDF 3477 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mohammadi, M., Moradi Hasan-Abad, A., Dehghani, P. et al. Dicentracin-Like from Asian sea bass Fish and Moronecidine-Like from Hippocampus Comes: Two Candidate Antimicrobial Peptides Against Leishmanina major Infection. Int J Pept Res Ther 27, 769–778 (2021). https://doi.org/10.1007/s10989-020-10125-4

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10989-020-10125-4

Keywords

Navigation