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leishmania parasites

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https://www.readbyqxmd.com/read/28428784/the-roles-of-mast-cells-in-parasitic-protozoan-infections
#1
REVIEW
Fangli Lu, Shiguang Huang
Protozoan parasites such as Plasmodium spp., Leishmania spp., Trypanosoma spp., and Toxoplasma gondii are major causes of parasitic diseases in both humans and animals. The immune system plays a critical role against protozoa, but their immune mechanism remains poorly understood. This highlights the need to investigate the function of immune cells involved in the process of parasite infections and the responses of host immune system to parasite infections. Mast cells (MCs) are known to be central players in allergy and anaphylaxis, and it has been demonstrated that MCs have crucial roles in host defense against a number of different pathogens, including parasites...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28427965/t1-st2-deficient-mice-display-protection-against-leishmania-infantum-experimental-infection
#2
Khalid Eltahir Khalid, Manuela Sales, Laís Sacramento, Diego L Costa, Djalma de Souza, Vanessa Carregaro, Joao Santana da Silva
T1/ST2 is a surface marker selectively expressed on type 2 helper (TH2) effector cells. As Leishmania infection in susceptible BALB/c mice have ascribed to a polarized TH2 response, this study aim to investigate the T1/ST2 (the receptor for IL-33), as a typical TH2 marker in the postulation that a shift towards a beneficial TH1 response would occur in the absence of ST2. For this, ST2 knockout (ST2(-/-)) and WT BALB/c mice were experimentally infected in the retro-orbital sinus with L. infantum. We showed that ST2(-/-) animals displayed better control of parasite burden in both spleen and liver tissues at different time points of chronic phases, and reduced spleenomegaly and hepatomegaly compared with the wild-type (WT) mice...
April 17, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28427904/leishmania-donovani-tyrosyl-trna-synthetase-structure-in-complex-with-a-tyrosyl-adenylate-analog-and-comparisons-with-human-and-protozoan-counterparts
#3
Ximena Barros-Álvarez, Keshia M Kerchner, Cho Yeow Koh, Stewart Turley, Els Pardon, Jan Steyaert, Ranae M Ranade, J Robert Gillespie, Zhongsheng Zhang, Christophe L M J Verlinde, Erkang Fan, Frederick S Buckner, Wim G J Hol
The crystal structure of Leishmania donovani tyrosyl-tRNA synthetase (LdTyrRS) in complex with a nanobody and the tyrosyl adenylate analog TyrSA was determined at 2.75 Å resolution. Nanobodies are the variable domains of camelid heavy chain-only antibodies. The nanobody makes numerous crystal contacts and in addition reduces the flexibility of a loop of LdTyrRS. TyrSA is engaged in many interactions with active site residues occupying the tyrosine and adenine binding pockets. The LdTyrRS polypeptide chain consists of two pseudo-monomers, each consisting of two domains...
April 17, 2017: Biochimie
https://www.readbyqxmd.com/read/28427438/canine-%C3%AE-defensin-1-cbd1-gene-as-a-possible-marker-for-leishmania-infantum-infection-in-dogs
#4
Lidiane Gomes da Silva, César Raimundo Lima Costa-Júnior, Carlos Alberto Santiago Figueiredo-Júnior, Tereza Cristina Leal-Balbino, Sergio Crovella, Domenico Otranto, Valdir de Queiroz Balbino, Filipe Dantas-Torres
BACKGROUND: Canine leishmaniasis caused by Leishmania infantum is a parasitic disease of great veterinary significance. Some dogs infected by L. infantum may mount a strong cellular immune response and clear the infection, while others may respond with exaggerated antibody production against the parasite and develop an overt disease, which may be fatal, if left untreated. The initial factors triggering the polarization of the immune response towards a predominantly T-helper 1 or T-helper 2 cytokines, as well as the markers of resistance and susceptibility to L...
April 20, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28426655/glycosome-biogenesis-in-trypanosomes-and-the-de-novo-dilemma
#5
REVIEW
Sarah Bauer, Meredith T Morris
Trypanosomatid parasites, including Trypanosoma and Leishmania, are the causative agents of lethal diseases threatening millions of people around the world. These organisms compartmentalize glycolysis in essential, specialized peroxisomes called glycosomes. Peroxisome proliferation can occur through growth and division of existing organelles and de novo biogenesis from the endoplasmic reticulum. The level that each pathway contributes is debated. Current evidence supports the concerted contribution of both mechanisms in an equilibrium that can vary depending on environmental conditions and metabolic requirements of the cell...
April 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28426153/a-non-pathogenic-recombinant-leishmania-expressing-lipophosphoglycan-3-against-experimental-infection-with-leishmania-infantum
#6
Leila Pirdel, Safar Farajnia
Visceral leishmaniasis (VL) is caused by Leishmania infantum in the Mediterranean basin and affects primarily children and immunosuppressed individuals. Various strategies of vaccination have so far been examined by either protein or DNA without achievable complete protection against the disease. The live non-pathogenic lizard parasite, Leishmania tarentolae, expressing elected Leishmania antigens has recently provided a promising new approach as a safe and effective live vaccine candidate to prevent leishmaniasis...
April 20, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28419151/skin-resident-cd4-t-cells-protect-against-leishmania-major-by-recruiting-and-activating-inflammatory-monocytes
#7
Nelson D Glennie, Susan W Volk, Phillip Scott
Tissue-resident memory T cells are required for establishing protective immunity against a variety of different pathogens, although the mechanisms mediating protection by CD4+ resident memory T cells are still being defined. In this study we addressed this issue with a population of protective skin-resident, IFNγ-producing CD4+ memory T cells generated following Leishmania major infection. We previously found that resident memory T cells recruit circulating effector T cells to enhance immunity. Here we show that resident memory CD4+ T cells mediate the delayed-hypersensitivity response observed in immune mice and provide protection without circulating T cells...
April 18, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28419136/occurrence-of-leishmania-infantum-in-the-central-nervous-system-of-naturally-infected-dogs-parasite-load-viability-co-infections-and-histological-alterations
#8
Valéria da Costa Oliveira, Viviane Cardoso Boechat, Artur Augusto Velho Mendes Junior, Maria de Fátima Madeira, Luiz Claudio Ferreira, Fabiano Borges Figueiredo, Monique Paiva Campos, Francisco das Chagas de Carvalho Rodrigues, Raquel de Vasconcellos Carvalhaes de Oliveira, Maria Regina Reis Amendoeira, Rodrigo Caldas Menezes
Zoonotic visceral leishmaniasis is caused by the protozoan Leishmania infantum and little is known about the occurrence and pathogenesis of this parasite in the CNS. The aims of this study were to evaluate the occurrence, viability and load of L. infantum in the CNS, and to identify the neurological histological alterations associated with this protozoan and its co-infections in naturally infected dogs. Forty-eight Leishmania-seropositive dogs from which L. infantum was isolated after necropsy were examined...
2017: PloS One
https://www.readbyqxmd.com/read/28415438/development-of-high-efficacy-peptide-coated-iron-oxide-nanoparticles-encapsulated-amphotericin-b-drug-delivery-system-against-visceral-leishmaniasis
#9
Rishikesh Kumar, Krishna Pandey, Ganesh C Sahoo, Susmita Das, Vnr Das, R K Topno, Pradeep Das
Visceral leishmaniasis, a protozoan disease transmitted by phlebotomine sandflies which affect mostly in Indian sub-continent. The treatment for visceral leishmaniasis (VL) caused by Leishmania donovani are limited and unsatisfactory. Currently available drug against such as miltefosine and polymer based drugs amBisome has high efficacy against VL but found serious side effects and poor absorbance. To overcome this, we developed peptide (glycine) coated iron oxide (Fe3O4) nanoparticles (GINPs) encapsulated amphoterecin B (AmB) drug against visceral leishmaniasis...
June 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28410591/eurasian-golden-jackal-as-host-of-canine-vector-borne-protists
#10
Barbora Mitková, Kristýna Hrazdilová, Gianluca D'Amico, Georg Gerhard Duscher, Franz Suchentrunk, Pavel Forejtek, Călin Mircea Gherman, Ioana Adriana Matei, Angela Monica Ionică, Aikaterini Alexandra Daskalaki, Andrei Daniel Mihalca, Jan Votýpka, Pavel Hulva, David Modrý
BACKGROUND: Jackals are medium-sized canids from the wolf-like clade, exhibiting a unique combination of ancestral morphotypes, broad trophic niches, and close phylogenetic relationships with the wolf and dog. Thus, they represent a potential host of several pathogens with diverse transmission routes. Recently, populations of the Eurasian golden jackal Canis aureus have expanded into the Western Palaearctic, including most of Europe. The aim of our study was to examine Eurasian golden jackals from Romania, Czech Republic and Austria for a wide spectrum of vector-borne protists and to evaluate the role of this species as a reservoir of disease for domestic dogs and/or humans...
April 14, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28407565/an-integrated-approach-towards-the-discovery-of-novel-non-nucleoside-leishmania-major-pteridine-reductase-1-inhibitors
#11
Franco Henrique Andrade Leite, Thamires Quadros Froes, Suellen Gonçalves da Silva, Evandro Italo Macêdo de Souza, Drielli Gomes Vital-Fujii, Gustavo Henrique Goulart Trossini, Samuel Silva da Rocha Pita, Marcelo Santos Castilho
Despite the fact that Leishmania ssp are pteridine auxotrophs, Dihydrofolate Reductase-Thymidylate Synthase (DHFR-TS) inhibitors are ineffective against Leishmania major. On the other hand Pteridine Reductase 1 (PTR1) inhibitors proved to be lethal to the parasite. Aiming at identifying hits that lie outside the chemical space of known PTR1 inhibitors, pharmacophore models that differentiate true-binders from decoys and explain the structure-activity relationships of known inhibitors were employed to virtually screen the lead-like subset of ZINC database...
March 27, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28406895/the-superfamily-keeps-growing-identification-in-trypanosomatids-of-ribj-the-first-riboflavin-transporter-family-in-protists
#12
Darío E Balcazar, María Cristina Vanrell, Patricia S Romano, Claudio A Pereira, Fernando A Goldbaum, Hernán R Bonomi, Carolina Carrillo
BACKGROUND: Trypanosomatid parasites represent a major health issue affecting hundreds of million people worldwide, with clinical treatments that are partially effective and/or very toxic. They are responsible for serious human and plant diseases including Trypanosoma cruzi (Chagas disease), Trypanosoma brucei (Sleeping sickness), Leishmania spp. (Leishmaniasis), and Phytomonas spp. (phytoparasites). Both, animals and trypanosomatids lack the biosynthetic riboflavin (vitamin B2) pathway, the vital precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) cofactors...
April 13, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28400285/development-and-evaluation-of-a-cedrol-loaded-nanostructured-lipid-carrier-system-for-in-vitro-and-in-vivo-susceptibilities-of-wild-and-drug-resistant-leishmania-donovani-amastigotes
#13
Nabanita Kar, Shreyasi Chakraborty, Asit Kumar De, Santanu Ghosh, Tanmoy Bera
Leishmaniasis is an epidemic in various countries, and the parasite Leishmania donovani is developing resistance against available drugs. In the present study the antileishmanial action of cedrol was evaluated in vitro and in vivo. Activity potentiation was achieved via nanostructured lipid carrier (NLC) complexation of cedrol. Cedrol-loaded NLC was prepared through the hot-melting emulsification-ultrasonication method. The cedrol- NLC prepared did not require the use of any organic solvents. The characterization of NLC-C1 and NLC-C2 revealed that particle size was 46...
April 8, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28397794/protein-malnutrition-promotes-dysregulation-of-molecules-involved-in-t-cell-migration-in-the-thymus-of-mice-infected-with-leishmania-infantum
#14
Monica Losada-Barragán, Adriana Umaña-Pérez, Sergio Cuervo-Escobar, Luiz Ricardo Berbert, Renato Porrozzi, Fernanda N Morgado, Daniella Areas Mendes-da-Cruz, Wilson Savino, Myriam Sánchez-Gómez, Patricia Cuervo
Protein malnutrition, the most deleterious cause of malnutrition in developing countries, has been considered a primary risk factor for the development of clinical visceral leishmaniasis (VL). Protein malnutrition and infection with Leishmania infantum leads to lymphoid tissue disorganization, including changes in cellularity and lymphocyte subpopulations in the thymus and spleen. Here we report that protein malnutrition modifies thymic chemotactic factors by diminishing the CCL5, CXCL12, IGF1, CXCL9 and CXCL10 protein levels in infected animals...
April 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28393067/biophysical-and-pharmacological-characterization-of-energy-dependent-efflux-of-sb-in-laboratory-selected-resistant-strains-of-leishmania-viannia-subgenus
#15
Priscila G Dos Reis, Rubens L do Monte-Neto, Maria N Melo, Frédéric Frézard
The growing resistance of leishmaniasis to first-line drugs like antimonials in some regions limits the control of this parasitic disease. The precise mechanisms involved in Leishmania antimony resistance are still subject to debate. The reduction of intracellular Sb(III) accumulation is a common change observed in both laboratory-selected and field isolated resistant Leishmania strains, but the exact transport pathways involved in antimony resistance have not yet been elucidated. In order to functionally characterize the antimony transport routes responsible for resistance, we performed systematic transport studies of Sb(III) in wild-type and resistant strains of L...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28390830/bmajpla2-ii-a-basic-lys49-phospholipase-a2-homologue-from-bothrops-marajoensis-snake-venom-with-parasiticidal-potential
#16
Amy N Grabner, Jorge Alfonso, Anderson M Kayano, Leandro S Moreira-Dill, Ana Paula de A Dos Santos, Cleópatra A S Caldeira, Juliana C Sobrinho, Ana Gómez, Fernando P Grabner, Fabio F Cardoso, Juliana Pavan Zuliani, Marcos R M Fontes, Daniel C Pimenta, Celeste Vega Gómez, Carolina B G Teles, Andreimar M Soares, Leonardo A Calderon
Snake venoms contain various proteins, especially phospholipases A2 (PLA2s), which present potential applications in diverse areas of health and medicine. In this study, a new basic PLA2 from Bothrops marajoensis with parasiticidal activity was purified and characterized biochemically and biologically. B. marajoensis venom was fractionated through cation exchange followed by reverse phase chromatographies. The isolated toxin, BmajPLA2-II, was structurally characterized with MALDI-TOF (Matrix-assisted laser desorption/ionization-time of flight) mass spectrometry, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), followed by two-dimensional electrophoresis, partial amino acid sequencing, an enzymatic activity assay, circular dichroism, and dynamic light scattering assays...
April 5, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28390095/the-anti-trichomonas-vaginalis-phloroglucinol-derivative-isoaustrobrasilol-b-modulates-extracellular-nucleotides-hydrolysis
#17
Camila Braz Menezes, Graziela Vargas Rigo, Henrique Bridi, Danielle da Silva Trentin, Alexandre José Macedo, Gilsane Lino Von Poser, Tiana Tasca
Trichomonas vaginalis causes trichomoniasis, a neglected sexually transmitted disease. Due to severe health consequences and treatment failure, new therapeutic alternatives are crucial. Phloroglucinols from Southern Brazilian Hypericum species demonstrated anti-T. vaginalis and anti-Leishmania amazonensis activities. The modulation of biochemical pathways involved in the control of inflammatory response by ectonucleotidases, NTPDase and ecto-5'-nucleotidase, represents new targets for combating protozoa. This study investigated the activity of phloroglucinol derivatives of Hypericum species from Southern Brazil against T...
April 8, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28389670/biochemical-analysis-of-leishmanial-and-human-gdp-mannose-pyrophosphorylases-and-selection-of-inhibitors-as-new-leads
#18
Wei Mao, Pierre Daligaux, Noureddine Lazar, Tâp Ha-Duong, Christian Cavé, Herman van Tilbeurgh, Philippe M Loiseau, Sébastien Pomel
Leishmaniases are an ensemble of diseases caused by the protozoan parasite of the genus Leishmania. Current antileishmanial treatments are limited and present main issues of toxicity and drug resistance emergence. Therefore, the generation of new inhibitors specifically directed against a leishmanial target is an attractive strategy to expand the chemotherapeutic arsenal. GDP-Mannose Pyrophosphorylase (GDP-MP) is a prominent therapeutic target involved in host-parasite recognition which has been described to be essential for parasite survival...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28389272/characterization-of-ciliobrevin-a-mediated-dynein-atpase-inhibition-on-flagellar-motility-of-leishmania-donovani
#19
G Srinivas Reddy, Aakash Gautam Mukhopadhyay, Chinmoy Sankar Dey
Axonemal dyneins are members of AAA+ proteins involved in force generation and are responsible for flagellar motility in eukaryotes. In this study, we characterized the effects of ciliobrevin A (CbA), a dynein ATPase inhibitor, on flagella driven motility of the protozoan parasite Leishmania donovani. Using fast-capture video microscopy, we observed that CbA decreased flagellar beat frequency of swimming parasites in a concentration-dependent manner. Beat frequency of live and reactivated L. donovani decreased by approximately 89% and 41% respectively in the presence of 250μM CbA...
April 5, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28386537/revealing-a-novel-otubain-like-enzyme-from-leishmania-infantum-with-deubiquitinating-activity-toward-k48-linked-substrate
#20
Clênia S Azevedo, Bruna C Guido, Jhonata L Pereira, Diego O Nolasco, Rafael Corrêa, Kelly G Magalhães, Flávia N Motta, Jaime M Santana, Philippe Grellier, Izabela M D Bastos
Deubiquitinating enzymes (DUBs) play an important role in regulating a variety of eukaryotic processes. In this context, exploring the role of deubiquitination in Leishmania infantum could be a promising alternative to search new therapeutic targets for leishmaniasis. Here we present the first characterization of a DUB from L. infantum, otubain (OtuLi), and its localization within parasite. The recombinant OtuLi (rOtuLi) showed improved activity on lysine 48 (K48)-linked over K63-linked tetra-ubiquitin (Ub) and site-directed mutations on amino acids close to the catalytic site (F82) or involved in Ub interaction (L265 and F182) caused structural changes as shown by molecular dynamics, resulting in a reduction or loss of enzyme activity, respectively...
2017: Frontiers in Chemistry
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