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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