Prediction of potential cysteine synthase inhibitors of Leishmania braziliensis and Leishmania major parasites by computational screening

Acta Tropica ◽  
2021 ◽  
pp. 106182
Author(s):  
Jair Téllez ◽  
Alejandra Amarillo ◽  
Carolina Suarez ◽  
Carlos Cardozo ◽  
Diego Guerra ◽  
...  
Keyword(s):  
Leishmania Major ◽  
Leishmania Braziliensis ◽  
Cysteine Synthase ◽  
Computational Screening

scholarly journals AVALIAÇÃO DA TERAPIA FOTODINÂMICA COM AZUL DE METILENO EM Leishmania major e Leishmania braziliensis: ESTUDO in vitro

2017 ◽  
Vol 22 (40) ◽  
pp. 649
Author(s):  
Danielle El Atra Coelho ◽  
Letícia Corrêa Fontana ◽  
Juliana Guerra Pinto ◽  
Juliana Ferreira-Strixino
Keyword(s):  
Leishmania Major ◽  
Leishmania Braziliensis

A Leishmaníase é uma doença crônica causada pelo protozoário do gênero Leishmania, cujo tratamento é agressivo. A Terapia Fotodinâmica (TFD) é uma alternativa promissora que combina luz, fotossensibilizador (FS) e oxigênio molecular, para causar a morte celular. O objetivo desse trabalho foi avaliar, in vitro, a ação da TFD com Azul de metileno (AM) em promastigotas de Leishmania, por teste de MTT, curva de crescimento e morfologia do parasito. O teste de MTT demonstrou alteração de ambas as espécies após interação com o AM no escuro e após TFD. A análise das curvas demonstrou que a TFD influenciou o crescimento das espécies. A análise morfológica revelou que o AM no escuro não causou alterações expressivas como a TFD, sendo a cepa de L. braziliensis mais afetada que a cepa de L. major. Pode-se concluir que a TFD com AM foi promissora contra promastigotas de Leishmania, pois foi capaz de diminuir o crescimento e alterar a morfologia dos parasitos em cultura.

scholarly journals Comparative and systems analyses of Leishmania spp. non-coding RNAs through developmental stages

2021 ◽  
Author(s):  
J. Eduardo Martinez-Hernandez ◽  
Victor Aliaga-Tobar ◽  
Carolina Gonzalez ◽  
Rubens Monte-Neto ◽  
Alberto J. M. Martin ◽  
...  
Keyword(s):  
Leishmania Major ◽  
Developmental Stages ◽  
Genomic Structure ◽  
Neglected Diseases ◽  
Leishmania Braziliensis ◽  
Functional Relationships ◽  
Host Interaction ◽  
Leishmania Spp ◽  
Non Coding Rnas ◽  
And Function

Leishmania spp. is the causal agent of several diseases called leishmaniases, neglected diseases that seek to be eradicated in the coming years. We aimed to study the genomic structure and function of non-coding RNAs (ncRNAs) from Leishmania spp. and to get insights into its RNAome. We studied 26 strains corresponding to 16 different species of Leishmania genus. RNAome analysis revealed the presence of several ncRNAs that are shared through different species, allowing us to differentiate between subgenus and as well as species that are canonically related to visceral leishmaniasis. We found coexpression relationships within coding genes and ncRNAs, thus suggesting possible functional relationships between different coding genes-ncRNAs. Expression analysis in the metacyclic developmental stage comparison for Leishmania braziliensis and Leishmania major reveals the presence of shared coexpressed ncRNAs to several other coding genes in both species involved in chromatin structure and host interaction. This work constitutes the first effort to characterize the Leishmania RNAome, supporting further approaches to better understand the role of ncRNAs in the gene regulation, infective process and host-parasite interaction.

scholarly journals Analysis of the Immune Responses of Mice to Infection with Leishmania braziliensis

1998 ◽  
Vol 66 (2) ◽  
pp. 827-829 ◽  
Author(s):  
Gregory K. DeKrey ◽  
Hermenio C. Lima ◽  
Richard G. Titus
Keyword(s):  
Immune Responses ◽  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Gamma Interferon ◽  
Interleukin 4 ◽  
Leishmania Braziliensis ◽  
Dependent Mechanism

ABSTRACT Leishmania major and Leishmania braziliensis both cause cutaneous leishmaniasis, but the former kills BALB/c mice while the latter is killed by the mice. This killing of L. braziliensis occurred by a gamma interferon-dependent mechanism, potentially made possible by the observed lack of high interleukin-4 production.

Photodynamic activity of Photogem® in Leishmania promastigotes and infected macrophages

2021 ◽  
Vol 16 (2) ◽  
pp. 95-106
Author(s):  
Juliana G Pinto ◽  
Luciana MC Marcolino ◽  
Juliana Ferreira-Strixino
Keyword(s):  
Photodynamic Therapy ◽  
Leishmania Major ◽  
Mitochondrial Activity ◽  
Leishmania Braziliensis ◽  
Morphological Alterations ◽  
Photodynamic Activity ◽  
Leishmania Promastigotes ◽  
Macrophage Viability

Objectives: This study aimed to evaluate the effect of photodynamic therapy (PDT) with Photogem® in promastigotes of Leishmania braziliensis and Leishmania major, and in infected macrophages. Materials & methods: The following parameters were analyzed: Photogem® internalization, mitochondrial activity, viability, tubulin marking and morphological alterations in promastigotes and viability in infected macrophages. Results: Photogem® accumulated in the cytosol and adhered to the flagellum. Changes were observed in the mitochondrial activity in groups maintained in the dark, with no viability alteration. After PDT, viability decreased up to 80%, and morphology was affected. Conclusion: The results point out that PDT with Photogem® can reduce parasite and macrophage viability.

scholarly journals Sensitive Molecular Diagnostics for Cutaneous Leishmaniasis

2017 ◽  
Vol 4 (2) ◽  
Author(s):  
Orli Sagi ◽  
Anat Berkowitz ◽  
Shlomi Codish ◽  
Victor Novack ◽  
Aviv Rashti ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Point Of Care ◽  
Leishmania Species ◽  
Rapid Diagnosis ◽  
Clinical Samples ◽  
Leishmania Braziliensis ◽  
Multiplex Qpcr ◽  
Highly Sensitive ◽  
Pcr Multiplex

Abstract Background Rapid diagnosis of cutaneous leishmaniasis (CL) and identification of Leishmania species is highly important for the disease management. In Israel, CL is caused mainly by Leishmania major and Leishmania tropica species. Methods We established an easy to handle point of care lesion-swabbing, combined with a highly sensitive multiplex real time PCR (multiplex qPCR) for accurate and rapid diagnosis of Leishmania species. Results Using three probes: one general for: Leishmania species, and two specific for L major, and L tropica, we screened 1783 clinical samples collected during two years. Leishmania species was found in 1086 individuals, 1008 L major, and 70 L tropica. Eight samples positive for Leishmania species only, were further tested using a second set of multiplex qPCR developed, and were found positive for Leishmania braziliensis and Leishmania infantum/donovani (2 and 6 samples, concomitantly). Conclusions Taken together, the test enabled diagnostics and better treatment of Leishmania infections from the Old World (1078 samples) and the New World (8 samples), and the subtyping of the dominant strains in the region, as well as in returning travelers’.

Glutathione protects macrophages and Leishmania major against nitric oxide-mediated cytotoxicity

Parasitology ◽  
1999 ◽  
Vol 118 (6) ◽  
pp. 559-566 ◽  
Author(s):  
P. R. T. ROMÃO ◽  
S. G. FONSECA ◽  
J. S. HOTHERSALL ◽  
A. A. NORONHA-DUTRA ◽  
S. H. FERREIRA ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Leishmania Major ◽  
Buthionine Sulfoximine ◽  
Trypanothione Reductase ◽  
Glutathione S Transferase ◽  
Total Glutathione ◽  
No Donor ◽  
Cysteine Synthase ◽  
Cytotoxic Effects ◽  
Ifn Γ

The aim of this investigation was to examine whether macrophage and Leishmania major glutathione were involved in either host or parasite protection against NO cytotoxicity. Buthionine sulfoximine (BSO), an inhibitor of γ-glutamyl-cysteine synthase, caused a complete and irreversible depletion of macrophage glutathione, but only a 20% and reversible decrease in L. major glutathione. Glutathione-depleted macrophages, when activated with IFN-γ/LPS, released less than 60% of the NO produced by untreated macrophages, resulting in a corresponding decrease in their leishmanicidal activity. BSO-treated macrophages were more susceptible to the cytotoxic effects of the NO donor SNAP. Treatment of macrophages with 1,3-bis(chloroethyl)-1-nitrosourea (BCNU), an inhibitor of glutathione reductase and trypanothione reductase or with Br-Octane, a glutathione-S-transferase substrate, resulted in a transient decrease in glutathione levels and did not increase the susceptibility of the macrophages to SNAP. Treatment of the promastigote forms of L. major with BCNU resulted in an 80% decrease in total glutathione concentration with no concomitant change in viability. However, this treatment rendered the parasites more susceptible to SNAP. Finally, macrophage glutathione protected the internalized L. major from SNAP. Overall, these results demonstrate that glutathione is an essential protective component against NO cytotoxicity on both macrophages and parasites.

scholarly journals Exploring the Possible Role of Nature in Curing Leishmaniasis

2019 ◽  
pp. 1-21
Author(s):  
Ravinder Sharma ◽  
Vikas Gupta ◽  
Viney Chawla ◽  
Pooja Chawla
Keyword(s):  
Natural Products ◽  
Leishmania Donovani ◽  
Leishmania Major ◽  
Chemotherapeutic Agents ◽  
Leishmania Braziliensis ◽  
Leishmania Chagasi ◽  
Major Health Problem ◽  
Major Health ◽  
Number Of Plant Species

Background: Communicable diseases have always been a threat to mankind since times immemorial. Leishmaniasis, an infectious disease caused by protozoan of various species of leishmania, is a major health problem spreading across 98 countries and about 350 million people stand the risk of this infection worldwide. Medical research has struggled a lot to combat this disease. Objective: Among the various approaches available for treatment of Leishmaniasis, many are costly so there is a need to develop effective but economical and easily available antileishmanial agents. Methods: Natural products are important source of various new medicaments and their derivatives can be used for synthetic modification and bioactivity optimization. Therefore, in order to fulfil the need for novel, economical, more effective and safer chemotherapeutic agents, scientists have explored Mother Nature in detail. Results: A number of plant species possess inhibitory activity against certain types of parasites such as Leishmania major, Leishmania amazonensis, Leishmania aethiopica, Leishmania braziliensis, Leishmania mexicana, Leishmania infantum, Leishmania chagasi and Leishmania donovani. Moreover natural products are economical, safer, more effective and without considerable side effects. Conclusion: The present review highlights the leishmanicidal activity of various natural products with an insight in to their possible mechanism.

scholarly journals Trypanosomatid Genomes Contain Several Subfamilies of ingi-Related Retroposons

2009 ◽  
Vol 8 (10) ◽  
pp. 1532-1542 ◽  
Author(s):  
Frédéric Bringaud ◽  
Matthew Berriman ◽  
Christiane Hertz-Fowler
Keyword(s):  
Trypanosoma Brucei ◽  
Leishmania Major ◽  
Trypanosoma Congolense ◽  
Leishmania Braziliensis ◽  
Site Specificity ◽  
Evolutionary Analysis ◽  
Trypanosoma Vivax ◽  
African Trypanosomes ◽  
Active Elements ◽  
Coding Capacity

ABSTRACT Retroposons are ubiquitous transposable elements found in the genomes of most eukaryotes, including trypanosomatids. The African and American trypanosomes (Trypanosoma brucei and Trypanosoma cruzi) contain long autonomous retroposons of the ingi clade (Tbingi and L1Tc, respectively) and short nonautonomous truncated versions (TbRIME and NARTc, respectively), as well as degenerate ingi-related retroposons devoid of coding capacity (DIREs). In contrast, Leishmania major contains only remnants of extinct retroposons (LmDIREs) and of short nonautonomous heterogeneous elements (LmSIDERs). We extend this comparative and evolutionary analysis of retroposons to the genomes of two other African trypanosomes (Trypanosoma congolense and Trypanosoma vivax) and another Leishmania sp. (Leishmania braziliensis). Three new potentially functional retroposons of the ingi clade have been identified: Tvingi in T. vivax and Tcoingi and L1Tco in T. congolense. T. congolense is the first trypanosomatid containing two classes of potentially active retroposons of the ingi clade. We analyzed sequences located upstream of these new long autonomous ingi-related elements, which code for the recognition site of the retroposon-encoded endonuclease. The closely related Tcoingi and Tvingi elements show the same conserved pattern, indicating that the Tcoingi- and Tvingi-encoded endonucleases share site specificity. Similarly, the conserved pattern previously identified upstream of L1Tc has also been detected at the same relative position upstream of L1Tco elements. A phylogenetic analysis of all ingi-related retroposons identified so far, including DIREs, clearly shows that several distinct subfamilies have emerged and coexisted, though in the course of trypanosomatid evolution, only a few have been maintained as active elements in modern trypanosomatid (sub)species.

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