leishmania spp
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Pathogens ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 92
Author(s):  
Cyrine Bouabid ◽  
Yoshiki Yamaryo-Botté ◽  
Sameh Rabhi ◽  
Haifa Bichiou ◽  
Chaima Hkimi ◽  
...  

Leishmaniasis is a protozoal vector-borne disease that affects both humans and animals. In the Mediterranean Basin, the primary reservoir hosts of Leishmania spp. are mainly rodents and canids. Lipidomic approaches have allowed scientists to establish Leishmania spp. lipid profiles for the identification of cell stage specific biomarkers, drug mechanisms of action, and host immune response. Using an in silico approach of global network interaction between genes involved in fatty acid (FA) synthesis followed by the GC-MS approach, we were able to characterize the fatty acid profiles of L. major derived from human and rodent hosts. Our results revealed that the lipid profile of L. major showed similarities and differences with those already reported for other Leishmania species. Phospholipids are the predominant lipid class. FA composition of rodent parasites was characterized by a lower abundance of the precursor C18:2(n-6). One of the rodent clones, which also expressed the lowest lipid abundance in PL and TAG, was the least sensitive clone to the miltefosine drug and has the lowest infection efficiency. Our findings suggest that the lipid composition variation may explain the response of the parasite toward treatment and their ability to infect their host.


2021 ◽  
Vol 7 (12) ◽  
pp. 118318-118328
Author(s):  
Brenda Maria Emanuela Silva Reis ◽  
Ana Karoline Silva Sousa ◽  
Raissa Drielle Freitas Franco ◽  
Dennis Leite dos Santos ◽  
Bárbara Ellen Brito Da Silva ◽  
...  
Keyword(s):  

Author(s):  
Jairo Alfonso Mendoza‐Roldan ◽  
Maria Stefania Latrofa ◽  
Viviana Domenica Tarallo ◽  
Ranju RS Manoj ◽  
Marcos Antonio Bezerra‐Santos ◽  
...  

2021 ◽  
Author(s):  
Jéssica C Paula ◽  
Nilma S Fernandes ◽  
Thaysa K Karam ◽  
Paula Baréa ◽  
Maria H Sarragiotto ◽  
...  

Background: Cutaneous leishmaniasis is caused by Leishmania spp., and its treatment is limited. The β-carbolines have shown activity against kinetoplastids. Aim: To evaluate the activity and effects of the β-carbolines, N-{2-[(4,6-bis(isopropylamino)-1,3,5-triazin-2-yl)amino]ethyl}-1-(4-methoxyphenyl)-β-carboline-3-carboxamide (RCC) and N-benzyl-1-(4-methoxy)phenyl-9H-beta-carboline-3-carboxamide (C5), against L. amazonensis intracellular amastigotes and to suggest their mechanism of action. Methods: We analyzed the activity and cytotoxicity of β-carbolines and the morphological alterations by electron microscopy. Mitochondrial membrane potential, production nitric oxide, reactive oxygen species, lipidic bodies, autophagic vacuoles and ATP were also evaluated. Results & conclusion: The results showed that RCC and C5 are active against intracellular amastigotes and were able to induce oxidative stress and ultrastructural alterations such as accumulation of lipid bodies and autophagic vacuoles, leading to parasite death.


2021 ◽  
Author(s):  
Nathalia Maria Barbosa da Silva ◽  
Fernanda Calvo Duarte ◽  
Márcia Cristina Mendes ◽  
Leonardo Costa Fiorini ◽  
Lucas Mello Morán ◽  
...  
Keyword(s):  

Introdução: Protozoários da espécie Leishmania spp. são causadores de diversas patologias infecciosas, atualmente, consideradas doenças negligenciadas pela Organização Mundial da Saúde (OMS). A Leishmaniose é transmitida pelo vetor flebotomíneo, inseto da família Psychodidae. O hospedeiro é infectado ao ser picado pela fêmea do vetor, conhecido popularmente como ‘’mosquito palha’’. O Brasil é palco destas doenças, sobretudo na região Norte e Nordeste, pois existe um tropismo do vetor, consequência do clima quente, onde adquiriram uma alta capacidade de adaptação. Nessa região, o acesso à saúde é mais precário, o que dificulta estudos e tratamentos. Existem variações da doença, que podem atingir desde humanos, animais silvestres e até cães domésticos. Não existem tratamentos específicos para suas variações. Quando há casos positivos em cães, o controle de zoonoses é acionado e o animal é eutanasiado. A justificativa é que eles são considerados reservatórios, e podem aumentar riscos de novas infecções. Objetivo: O estudo in silico é um meio promissor para encontrar inibidores específicos, como moléculas sintéticas e fármacos, com o propósito de paralisar o ciclo de vida do parasita, por meio da inibição das moléculas de interesse. A telomerase é uma enzima envolvida na síntese de DNA, primordial para a manutenção dos telômeros (estruturas finais dos cromossomos), que têm função de proteger o material genético contra danos. Este trabalho em andamento tem como propósito analisar inibidores da telomerase para o controle de doenças. Materiais e métodos: Foram selecionados artigos científicos em bancos de dados dos sites PubVet e Scielo, com palavras chave e posterior revisão bibliográfica. Os artigos selecionados foram catalogados com critérios de inclusão mais relevante. Resultados: Foram encontradas inibidores da proteína Hsp90, que são conhecidos por sua ação antiparasitária. Essa proteína é primordial para o desenvolvimento de vida do protozoário, pois fazem parte de seu desenvolvimento celular. Os resultados obtidos mostraram que esses inibidores são promissores para a indução da morte do parasita. Conclusão: A pesquisa ainda está em andamento, mas a piori, é notório a importância do estudo sobre a Leishmaniose, assim como outras doenças, para novos tratamentos e sua erradicação.


2021 ◽  
Author(s):  
Sandra Alves de Araújo ◽  
Tatiane Aranha da Penha-Silva ◽  
Jaqueline Diniz Pinho ◽  
Marcelo de Souza Andrade ◽  
Ana Lucia Abreu-Silva

Leishmaniasis is an infectious and parasitic disease of great importance in public health. Numerous studies indicate that biochemical and molecular mechanisms are factors that contribute to the emergence of antileishmanial drug resistance. Currently, miRNAs have been identified as targets for the invasion of pathogens to control the immune response and imply resistance to treatments. Considering the alarming growth in drug resistance, new possibilities for controlling leishmaniasis have been emerging. Natural compounds originating from medicinal plants are being increasingly explored as promising antileishmanial alternatives. The chapter aims to provide a brief review on mechanisms of action associated with traditional agents used to treat leishmaniasis, focusing mainly on molecular bases associated with the resistance of Leishmania spp. to current drugs and identifying the possible miRNAs involved in this process. In addition, we seek to describe some of the promising plant molecules that can be used as potential antileishmanial agents and their possible mechanisms of action.


Author(s):  
Maira Alemán Santos ◽  
Lina Martínez-Pérez ◽  
Matilde Rivero-Rodríguez ◽  
Luis Cortés-Alemán ◽  
Alveiro Pérez-Doria ◽  
...  

Introducción: Aunque la leishmaniasis visceral (LV) es endémica en el Caribe colombiano, en los últimos años se ha observado un incremento en su área de distribución, con el registro de casos en nuevas localidades. Objetivos: En este estudio se caracterizaron los flebotomíneos, parásitos del género Leishmania y algunos vertebrados domésticos asociados al primer caso humano de LV en la vereda Toro, San Juan Nepomuceno, Bolívar, Colombia. Metodología: Los insectos fueron sometidos a extracción, amplificación y secuenciación de ADN para establecer si estaban infectados con Leishmania spp. e identificar sus ingestas sanguíneas. Adicionalmente, en los caninos se determinaron los títulos de anticuerpos anti-Leishmania mediante la técnica de inmunofluorescencia indirecta. Resultados: En total se recolectaron 2178 flebotomíneos, el 99,6% de los cuales fue identificado como Lutzomyia evansi. Los parásitos Leishmania infantum y Leishmania braziliensis fueron detectados en esta especie, con una frecuencia mínima de infección de 0,003% (3/1070) y 0,0009% (1/1070), respectivamente. El 16,73% de las hembras de Lu. evansi se encontraron alimentadas de Homo sapiens sapiens, el 16,32% de  Capra hircus , el 12,45% de Sus scrofa domesticus, el 11,63 % de Bos indicus y el 9,79% de Canis familiaris. Uno de ocho caninos serológicamente evaluados fue positivo para leishmaniasis canina. Conclusión: El hallazgo en Lu. evansi de ingestas de sangre mixtas de humanos y caninos, evidencia el vínculo epidemiológico entre las Lutzomyia infectados con el parásito, los potenciales reservorios y la población humana, lo que explicaría la aparición del primer caso de LV en esta localidad del Caribe colombiano.


2021 ◽  
Vol 22 (22) ◽  
pp. 12592
Author(s):  
Miriam Algarabel ◽  
Celia Fernández-Rubio ◽  
Katerina Musilova ◽  
José Peña-Guerrero ◽  
Andrés Vacas ◽  
...  

Leishmaniasis is a neglected tropical disease caused by Leishmania spp. The improvement of existing treatments and the discovery of new drugs remain ones of the major goals in control and eradication of this disease. From the parasite genome, we have identified the homologue of the human oncogene PES1 in Leishmania major (LmjPES). It has been demonstrated that PES1 is involved in several processes such as ribosome biogenesis, cell proliferation and genetic transcription. Our phylogenetic studies showed that LmjPES encodes a highly conserved protein containing three main domains: PES N-terminus (shared with proteins involved in ribosomal biogenesis), BRCT (found in proteins related to DNA repair processes) and MAEBL-type domain (C-terminus, related to erythrocyte invasion in apicomplexan). This gene showed its highest expression level in metacyclic promastigotes, the infective forms; by fluorescence microscopy assay, we demonstrated the nuclear localization of LmjPES protein. After generating mutant parasites overexpressing LmjPES, we observed that these clones displayed a dramatic increase in the ratio of cell infection within macrophages. Furthermore, BALB/c mice infected with these transgenic parasites exhibited higher footpad inflammation compared to those inoculated with non-overexpressing parasites.


Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2305
Author(s):  
Alexei Y. Kostygov ◽  
Danyil Grybchuk ◽  
Yulia Kleschenko ◽  
Daniil S. Chistyakov ◽  
Alexander N. Lukashev ◽  
...  

Leishmania spp. are important pathogens causing a vector-borne disease with a broad range of clinical manifestations from self-healing ulcers to the life-threatening visceral forms. Presence of Leishmania RNA virus (LRV) confers survival advantage to these parasites by suppressing anti-leishmanial immunity in the vertebrate host. The two viral species, LRV1 and LRV2 infect species of the subgenera Viannia and Leishmania, respectively. In this work we investigated co-phylogenetic patterns of leishmaniae and their viruses on a small scale (LRV2 in L. major) and demonstrated their predominant coevolution, occasionally broken by intraspecific host switches. Our analysis of the two viral genes, encoding the capsid and RNA-dependent RNA polymerase (RDRP), revealed them to be under the pressure of purifying selection, which was considerably stronger for the former gene across the whole tree. The selective pressure also differs between the LRV clades and correlates with the frequency of interspecific host switches. In addition, using experimental (capsid) and predicted (RDRP) models we demonstrated that the evolutionary variability across the structure is strikingly different in these two viral proteins.


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