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Table 1 Anti-microbial effects of melittin against various protozoan parasites. Developmental forms of tested protozoa, methodologies, and key findings of the relevant studies have also been included

From: Melittin as a promising anti-protozoan peptide: current knowledge and future prospects

Protozoan parasites Identifier Developmental forms Methods Key findings References
Leishmania donovani S-2 strain Promastigotes Evaluation of Ca2+ influx by fluorescence measurements Dose-dependent induction of Ca2+ influx across the plasma membrane
Inhibition of melittin-induced Ca2+ influx by OBAA
Catisti et al. (2000)
  R9 strain Promastigotes Cell viability analysis using MTT assay High killing activity against promastigotes (LD50: 0.3 μM) Díaz-Achirica et al. (1998)
  Not mentioned Autoclaved promastigotes Measurements of sLA-induced cytokines in the collected whole blood samples from mice receiving melittin-adsorbed autoclaved L. donovani Significant reductions in the mean levels of IL-10 (p = 0.00001), IFN-γ (p = 0.00008) and TNF-α (p = 0.000001) in comparison to the control (non-treated) group Eltahir Saeed and Khalil (2017)
Leishmania infantum MHOM/BR/1972/LD strain Amastigotes and promastigotes Cell viability analysis using MTT assay, quantification of cytokines, and determination of NO and H2O2 production Direct inhibition of both amastigotes and promastigotes
Indirect inhibition of intracellular amastigotes by immunomodulatory effects on macrophages (increasing IL-12 production and decreasing the levels of IL-10, TNF- α, NO, and H2O2)
Pereira et al. (2016)
Leishmania major Not mentioned Promastigotes Cell viability analysis using microplate Alamar blue assay Induction of death in 50% of promastigotes at 74.01 ± 1.27 μg/mL Pérez-Cordero et al. (2011)
Leishmania panamensis Not mentioned Promastigotes Cell viability analysis using microplate Alamar blue assay Ineffectiveness of melittin in killing 50% of promastigotes at > 100 μg/mL Pérez-Cordero et al. (2011)
Plasmodium berghei ANKA strain Ookinetes
and gametocytes
Analysis of the effects of melittin on ookinetes (in vitro) and sporogonic stages (Anopheles stephensi) of the parasite Complete obliteration of ookinetes after 30 min
Significant reductions in both infection prevalence (p = 0.019) and infection intensity (p < 0.001) compared to those in control mosquitoes
Carter et al. (2013)
Plasmodium falciparum NF54 strain Gametocytes Analysis of the effects of melittin and multi-melittin arrays on sporogonic stages of Anopheles coluzzii Significant reductions of infection intensity (p < 0.001) in mosquitoes fed on cultured P. falciparum spiked with melittin (native or modified peptide) compared to those in control mosquitoes Habtewold et al. (2019)
  NF54 strain Gametocytes Analysis of the effects of melittin on sporogonic stages of Anopheles gambiae Significant decrements in both infection prevalence (p < 0.001) and infection intensity (p = 0.019) compared to those in control mosquitoes Carter et al. (2013)
Toxoplasma gondii RHβ strain Extracellular tachyzoites β-galactosidase release assay for the assessment of lytic activity Induction of cytosolic β-galactosidase release and cell lysis Seeber, (2000)
Trypanosoma brucei brucei M110 clone Bloodstream forms Evaluation of Ca2+ influx by fluorescence measurements Dose-dependent induction of Ca2+ influx across the plasma membrane Ruben et al. (1996)
  AnTat1.1E clone Procyclic forms Evaluation of Ca2+ movement between organelles by luminescence measurements Transient retention of Ca2+ in mitochondria
Contribution of acidic compartments to Ca2+ homeostasis during the signaling process
Xiong et al. (1997)
  ILTar 1 procyclics Trypomastigotes Evaluation of Ca2+ influx by fluorescence measurements Dose-dependent induction of Ca2+ influx across the plasma membrane
Inhibition of melittin effects on Ca2+ influx by OBAA, a PLA2 inhibitor
Induction of Ca2+ release from intracellular stores in the absence of CaCl2 (and in the presence of 1 mM EGTA)
Catisti et al. (2000)
Trypanosoma cruzi Y strain Amastigotes Evaluation of Ca2+ influx by fluorescence measurements Induction of Ca2+ influx
Inhibition of melittin effects on Ca2+ influx by OBAA
Catisti et al. (2000)
  macrophagotropic Tehuantepec strain Trypomastigotes Light, fluorescence, and electron microscopies, evaluation of trypanocidal activity, and measurement of β-galactosidase release (before and after parasitic infection) Inhibition of the parasite motility
Disruption of plasma membrane
Reduction of the parasite infectivity
No reduction in the growth of intracellular parasites
Jacobs et al. (2003)
  M/HOM/AR/74/CA-I CL72 Trypomastigotes Determination of lethal concentration, evaluation of T. cruzi killing by dual peptide treatment, and recovery of AMP-treated cells after transfer to non-AMP containing media High killing activity against Trypanosoma cruzi
Synergistic and additive anti-parasitic effects of melittin in combination with certain AMPs
Inability of the parasite to recover after treatment with 10 μM of melittin
Fieck et al. (2010)
  CL Brener clone Epimastigotes and trypomastigotes Evaluation of the parasite viability, flow cytometry analysis, and TEM Dose-dependent decrease in the number of T. cruzi cells
Permeabilization of protozoan cell membrane (High percentages of PI-labeled epimastigotes and trypomastigotes)
Induction of autophagy (epimastigotes) and apoptosis (trypomastigotes)
Adade et al. (2012)
  CL Brener clone Amastigotes, epimastigotes, and trypomastigotes Evaluation of the parasite viability, treatment during the T. cruzi intracellular cycle, PI uptake assay, evaluation of mitochondrial membrane potential, TUNEL assay, SEM, TEM, and fluorometric analysis of MDC Induction of growth inhibition or killing of developmental forms of the parasite (< 2.5 μg/mL)
Induction of structural changes (plasma membrane blebbing, mitochondrial swelling, and nuclear alterations)
Induction of alterations in ΔΨm
Disorganization of the kinetoplast DNA filaments
Induction of alterations in flagellar structure
Permeabilization of cell membrane
Induction of apoptosis and autophagy
Adade et al. (2013)
  1. ΔΨm Mitochondrial membrane potential, AMP Anti-microbial peptide, EGTA Ethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid, H2O2 Hydrogen peroxide, IFN-γ Interferon-γ, IL-10 Interleukin-10, IL-12 Interleukin-12, LD50 Half lethal dose, MDC Monodansylcadaverine, MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, NO Nitric oxide, OBAA 3-(4-octadecyl)-benzoylacrylic acid; PI Propidium iodide, PLA2 Phospholipase A2, SEM Scanning electron microscopy; sLA: Soluble Leishmania donovani antigen, TEM Transmission electron microscopy, TNF-α Tumor necrosis factor-α, TUNEL Terminal deoxynucleotidyl transferase (TDT)-mediated dUTP-biotin nick end-labeling