Suicidal Leishmania

Podešvová, Lucie; Leštinová, Tereza; Horáková, Eva; Lukeš, Julius; Volf, Petr; Yurchenko, Vyacheslav

doi:10.3390/pathogens9020079

Cited by 7 publications

(5 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The authors stated that such a deliberately attenuated parasite may be used to vaccinate the host, because its viability is controlled by toxin stabilization, resulting in a significantly reduced pathogenesis. 28 Evaluation of α-toxin IC 50 in our study showed that there is a significant difference between the mean number of amastigotes from 100 macrophages in groups exposed to α-toxin plus glucantime in comparison with negative control. As the strong fatal effect of the two mentioned components on cultivated Leishmania parasites was found at lower optimal concentrations (0.03 ± 0.002 µg/mL) compared with glucantime plus non-toxic α-toxin or each of them alone.…”

Section: Discussionmentioning

confidence: 60%

Evaluation of the Anti-Leishmanial Effect of Recombinant Clostridium α-Toxin

Namdar¹,

Khanahmad²,

Ghayour³

et al. 2020

IDR

View full text Add to dashboard Cite

Background: Leishmaniasis is an infectious disease common in tropical and subtropical regions caused by the genus Leishmania, which is transmitted by the bite of female sandflies. In this study, we evaluate the anti-leishmanial effect of recombinant Clostridium α-toxin protein alone and the combination with glucantime through in vitro and in vivo. Materials and Methods: Production, expression, and purification of recombinant α-toxin were evaluated by SDS-PAGE and Western blotting techniques. The antileishmanial activities of the purified α-toxin plus and without glucantime were examined in vitro and in vivo. Results: The results indicated successful expression of α-toxin as a 48 kDa band on SDS-PAGE and Western blot methods. Also, evaluation of α-toxin IC 50 showed the strong fatal effect of it, and glucantime on medium proliferated Leishmania promastigotes at lower concentrations compared with glucantime or α-toxin alone. Moreover, in vivo surveys showed that at the end of treatment courses, the mean of lesion size diminished in glucantime plus α-toxin treated mice versus negative control groups (p < 0.001). Also, there was a significant difference in the parasite burden of the spleen and liver of the control versus the test groups (p < 0.001). Conclusion: The results showed recombinant α-toxin has synergistic effects with glucantime in destroying Leishmania parasites.

show abstract

Section: Discussionmentioning

confidence: 60%

Evaluation of the Anti-Leishmanial Effect of Recombinant Clostridium α-Toxin

Namdar¹,

Khanahmad²,

Ghayour³

et al. 2020

IDR

View full text Add to dashboard Cite

show abstract

“…So, a PLA2 from B. jararacussu venom encapsulated in liposomes displays therapeutic effectiveness comparable to that of known antiparasitic Glucantime in a cutaneous leishmaniasis mouse model [ 70 ]. A fairly original construct has been developed based on the expression of a PLA2 from the B. pauloensis venom in a leishmanial “suicidal” strain, which leads to the inducible death of the parasite cells in vitro [ 71 ]. The approach that also should be mentioned here is to identify in the toxin molecule the fragments of amino acid sequence responsible for interaction with the target in protozoa, followed by the synthesis of these relatively short peptides and their further use as antiprotozoals.…”

Section: Discussionmentioning

confidence: 99%

The Potassium Channel Blocker β-Bungarotoxin from the Krait Bungarus multicinctus Venom Manifests Antiprotozoal Activity

et al. 2023

View full text Add to dashboard Cite

Protozoal infections are a world-wide problem. The toxicity and somewhat low effectiveness of the existing drugs require the search for new ways of protozoa suppression. Snake venom contains structurally diverse components manifesting antiprotozoal activity; for example, those in cobra venom are cytotoxins. In this work, we aimed to characterize a novel antiprotozoal component(s) in the Bungarus multicinctus krait venom using the ciliate Tetrahymena pyriformis as a model organism. To determine the toxicity of the substances under study, surviving ciliates were registered automatically by an original BioLaT-3.2 instrument. The krait venom was separated by three-step liquid chromatography and the toxicity of the obtained fractions against T. pyriformis was analyzed. As a result, 21 kDa protein toxic to Tetrahymena as isolated and its amino acid sequence was determined by MALDI TOF MS and high-resolution mass spectrometry. It was found that antiprotozoal activity was manifested by β-bungarotoxin (β-Bgt) differing from the known toxins by two amino acid residues. Inactivation of β-Bgt phospholipolytic activity with p-bromophenacyl bromide did not change its antiprotozoal activity. Thus, this is the first demonstration of the antiprotozoal activity of β-Bgt, which is shown to be independent of its phospholipolytic activity.

show abstract

“…Promastigotes and amastigotes are physiologically different in their sensitivity to drugs, with amastigotes having the greater capability to accumulate drugs [75]. Furthermore, Podešvová et al [52] reported that variations in the compositions of parasite membranes could also be responsible for the differences in the activities of snake venoms and their fractions. Additionally, mechanisms including post-translational modifications, protein stability, and folding may likely influence toxin activity on parasites [52].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, Borges et al [29] and Borges et al [30] reported that PLA2s of B. pauloensis inhibited parasite adhesion, intracellular proliferation, parasite viability, intracellular proliferation and proinflammatory cytokine production in T. gondii. Furthermore, the PLA2s of B. pauloensis induced in vitro cell death in L. mexicana [52], and Zieler et al [72] reported that the PLA2s of C. adamanteus blocked the ookinete adhesion and oocyst formation of both P. gallinaceum and P. falciparum. According to a previous study [63], crotoxin B and its complex from C. durissus cumanensis exerted a cytotoxic effect against the mononuclear cells of P. falciparum, and another [19] reported that the crovirin from C. viridis could inhibit and lyse humaninfective trypanosome species, including the intracellular amastigotes.…”

Section: Antiprotozoal Effect Of Snake Venom Components or Fractionsmentioning

confidence: 99%

“…Their isoform diversity often presents in their venom, likely facilitating synergistic effects such as a simultaneous action on multiple steps of the blood-clotting cascade [1]. Reports [27,52,54] showed the antiprotozoal activities of a metalloproteinase from the Bothrops species on T. gondii, and P. falciparum, which is one of the most threatening and widespread species.…”

Section: Antiprotozoal Effect Of Snake Venom Components or Fractionsmentioning

confidence: 99%

See 1 more Smart Citation

Antiprotozoal Effect of Snake Venoms and Their Fractions: A Systematic Review

Abdullahi

Musa

et al. 2021

Pathogens

View full text Add to dashboard Cite

Background: Protozoal infection is a lingering public health issue of great concern, despite efforts to produce drugs and vaccines against it. Recent breakthrough research has discovered alternative antiprotozoal agents encompassing the use of snake venoms and their components to cure these infections. This study collated the existing literature to examine the antiprotozoal effect of snake venoms and their fractions. Methods: We conducted a systematic review following the PRISMA guidelines. The PubMed and Embase databases were searched from their inception until 13 October 2021. Articles were screened at the title, abstract and full-text phases. Some additional studies were obtained through the manual search process. Results: We identified 331 studies via the electronic database and manual searches, of which 55 reporting the antiprotozoal effect of snake venoms and their components were included in the review. Around 38% of studies examined the effect of whole crude venoms, and a similar percentage evaluated the effect of a proportion of enzymatic phospholipase A2 (PLA2). In particular, this review reports around 36 PLA2 activities and 29 snake crude venom activities. We also report the notable phenomenon of synergism with PLA2 isoforms of Bothrops asper. Importantly, limited attention has been given so far to the antiprotozoal efficacies of metalloproteinase, serine protease and three-finger toxins, although these venom components have been identified as significant components of the dominant venom families. Conclusion: This study highlights the impact of snake venoms and their fractions on controlling protozoal infections and suggests the need to examine further the effectiveness of other venom components, such as metalloproteinase, serine protease and three-finger toxins. Future research questions in this field must be redirected toward synergism in snake venom components, based on pharmacological usage and in the context of toxicology. Ascertaining the effects of snake venoms and their components on other protozoal species that have not yet been studied is imperative.

show abstract

Suicidal Leishmania

Cited by 7 publications

References 49 publications

<p>Evaluation of the Anti-Leishmanial Effect of Recombinant <em>Clostridium</em> α-Toxin</p>

<p>Evaluation of the Anti-Leishmanial Effect of Recombinant <em>Clostridium</em> α-Toxin</p>

The Potassium Channel Blocker β-Bungarotoxin from the Krait Bungarus multicinctus Venom Manifests Antiprotozoal Activity

Antiprotozoal Effect of Snake Venoms and Their Fractions: A Systematic Review

Contact Info

Product

Resources

About