Comparative study of different forms of Jellein antimicrobial peptide on Leishmania parasite

Exp Parasitol. 2020 Feb:209:107823. doi: 10.1016/j.exppara.2019.107823. Epub 2019 Dec 17.

Abstract

Typically, antimicrobial peptides (AMPs) are short positive charged peptides serving a key role in innate immunity as well as antimicrobial activity. Discovering novel therapeutic agents is considered as an undeniable demand due to increasing microbial species with antibiotic resistance. In this direction, the unique ability of AMPs to modulate immune responses highlighted them as novel drug candidates in the field of microbiology. Patients affected by leishmaniasis; a neglected tropical disease, confront serious problems for their treatment including resistance to common drugs as well as toxicity and high cost of therapy. So, there is a need for development of new drug candidates to control the diseases. Jellein, a peptide derived from royal jelly of honeybee has been shown to have promising effect against several bacterial and fungal species. In current study, anti-leishmanial effect of Jellein and its lauric acid conjugated form was investigated against two forms of Leishmania major (L. major) parasite. Moreover, cytotoxic effect of these peptides was studied in THP1 cell line and human Red Blood Cells (RBCs). Furthermore, the mechanism of action of peptides on L. major promastigotes was assessed through different methods. The results demonstrated that, conjugation of lauric acid to Jellein not only had no effect on the elevation of antimicrobial activity but also halted it completely. Moreover, Jellein caused a limitation in the number of L. major promastigotes by pore formation as well as changing the membrane potential rather than induction of apoptosis or activation of caspases.

Keywords: Acylation; Antimicrobial peptide; Leishmaniasis; Therapeutics.

MeSH terms

  • Antigens, Differentiation, B-Lymphocyte / pharmacology
  • Antimicrobial Cationic Peptides / pharmacology*
  • Antimicrobial Cationic Peptides / therapeutic use
  • Antimicrobial Cationic Peptides / toxicity
  • Antiprotozoal Agents / pharmacology*
  • Antiprotozoal Agents / therapeutic use
  • Antiprotozoal Agents / toxicity
  • Caspases / drug effects
  • Caspases / metabolism
  • Cell Line, Tumor
  • Cell Membrane Permeability / drug effects
  • Erythrocytes / drug effects
  • Escherichia coli / drug effects
  • Fatty Acids / chemistry
  • Flow Cytometry
  • Hemolysis
  • Histocompatibility Antigens Class II / pharmacology
  • Humans
  • Lauric Acids / pharmacology
  • Lauric Acids / therapeutic use
  • Lauric Acids / toxicity
  • Leishmania major / drug effects*
  • Leishmania major / ultrastructure
  • Leishmaniasis, Cutaneous / drug therapy*
  • Membrane Potentials / drug effects
  • Microscopy, Electron, Scanning
  • Neglected Diseases / drug therapy
  • Neglected Diseases / parasitology
  • Oligopeptides / chemistry*
  • Oligopeptides / pharmacology
  • Oligopeptides / therapeutic use
  • Oligopeptides / toxicity

Substances

  • Antigens, Differentiation, B-Lymphocyte
  • Antimicrobial Cationic Peptides
  • Antiprotozoal Agents
  • Fatty Acids
  • Histocompatibility Antigens Class II
  • Jelleine I
  • Jelleine II
  • Jelleine III
  • Lauric Acids
  • Oligopeptides
  • invariant chain
  • lauric acid
  • Caspases
  • royal jelly