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Leishmania

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https://www.readbyqxmd.com/read/28431354/first-example-of-peptides-targeting-the-dimer-interface-of-leishmania-infantum-trypanothione-reductase-with-potent-in%C3%A2-vitro-antileishmanial-activity
#1
Marta Ruiz-Santaquiteria, Pedro A Sánchez-Murcia, Miguel A Toro, Héctor de Lucio, Kilian Jesús Gutiérrez, Sonia de Castro, Filipa A C Carneiro, Federico Gago, Antonio Jiménez-Ruiz, María-José Camarasa, Sonsoles Velázquez
A series of 9-mer and 13-mer amide-bridged cyclic peptides derived from the linear prototype Ac-PKIIQSVGIS-Nle-K-Nle-NH2 (Toro et al. ChemBioChem2013) has been designed and synthesized by introduction of the lactam between amino acid side chains that are separated by one helical turn (i, i+4). All of these compounds were tested in vitro as both dimerization and enzyme inhibitors of Leishmania infantum trypanothione reductase (Li-TryR). Three of the 13-mer cyclic peptide derivatives (3, 4 and 6) inhibited the oxidoreductase activity of Li-TryR in the low micromolar range and they also disrupted enzyme dimerization...
April 13, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28429896/production-of-a-conjugate-between-the-rk346-antigen-from-leishmania-infantum-and-the-horseradish-peroxidase-c-for-the-detection-of-rk346-antibodies
#2
Juan Rengifo-González, Yollyseth Medina-Mora, Sasha Silva-Barrios, María Elizabeth Márquez-Contreras, María Tibisay Ruiz, Ana J Cáceres, Juan Luis Concepción, Wilfredo Quiñones
It was designed and characterized a reporter system to be captured by an- tibodies bound to ELISA plates. The system was designed with the rK346 from Leishmania infantum, a highly antigenic and specific protein. The rK346 was coupled to the horseradish peroxidase C (HRPc) from Armoracia rusticana using glutaraldehyde or sulfo-SMCC. Gluta- raldehyde conjugation was performed in two steps. Separation of conjugates was carried out using a Sepharose S-200 in size exclusion chromatography (SEC); fractions were analyzed via HRPc activity and through ELISA plates sensitized with polyclonal anti-rK346 IgG puri- fied from rabbit serum...
June 2016: Investigación Clínica
https://www.readbyqxmd.com/read/28428784/the-roles-of-mast-cells-in-parasitic-protozoan-infections
#3
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
#4
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/28427957/pcr-based-identification-of-trypanosoma-lewisi-and-trypanosoma-musculi-using-maxicircle-kinetoplast-dna
#5
Xiao-Kun Hong, Xuan Zhang, Octavio Alejandro Fusco, You-Gen Lan, Zhao-Rong Lun, De-Hua Lai
Trypanosoma lewisi, transmitted by rat fleas, is a widespread pathogen specific to rats with records of human infection cases. Its closely related species with global distribution, Trypanosoma musculi, is transmitted between mice by ingestion of infected fleas. These trypanosomes are of similar morphology, making it difficult to distinguish them by microscopy. In this study, we have developed a rapid, sensitive and reliable PCR method for the diagnosis of T. lewisi and T. musculi. The T. lewisi-specific amplicons were not produced by other Trypanosoma, such as T...
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
#6
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
#7
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
#8
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
#9
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/28423167/what-pre-columbian-mummies-could-teach-us-about-south-american-leishmaniases
#10
Denis Sereno, Mohammad Akhoundi, Franck Dorkeld, Bruno Oury, Hooman Momen, Pascale Perrin
A recent report on the taxonomic profile of the human gut microbiome in pre-Columbian mummies (Santiago-Rodriguez et al. 2016) gives for the first time evidence of the presence of Leishmania DNA (sequences similar to Leishmania donovani according to the authors) that can be reminiscent of visceral leishmaniasis during the pre-Columbian era. It is commonly assumed that Leishmania infantum, the etiological agent of American visceral leishmaniasis (AVL) was introduced into the New World by the Iberian conquest...
April 1, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28421410/antiparasitic-sesquiterpenes-from-the-cameroonian-spice-scleria-striatinux-and-preliminary-in-vitro-and-in-silico-dmpk-assessment
#11
Kennedy D Nyongbela, Fidele Ntie-Kang, Thomas R Hoye, Simon M N Efange
The antiparasitic activity and preliminary in vitro and in silico drug metabolism and pharmacokinetic (DMPK) assessment of six isomeric sesquiterpenes (1-6), isolated from the Cameroonian spice Scleria striatinux De Wild (Cyperaceae) is reported. The study was prompted by the observation that two of the compounds (1 and 2) exhibited varying levels of antiparasitic activity on Plasmodium falciparum, Trypanosoma brucei rhodesiense, Trypanosoma cruzi and Leishmania donovani. The in silico method employed a total of 46 descriptors, calculated using Schrödinger QikProp software...
April 18, 2017: Natural Products and Bioprospecting
https://www.readbyqxmd.com/read/28419151/skin-resident-cd4-t-cells-protect-against-leishmania-major-by-recruiting-and-activating-inflammatory-monocytes
#12
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
#13
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/28416006/leishmania-major-large-rab-gtpase-is-highly-immunogenic-in-individuals-immune-to-cutaneous-and-visceral-leishmaniasis
#14
Rym Chamakh-Ayari, Mehdi Chenik, Ahmed Sahbi Chakroun, Narges Bahi-Jaber, Karim Aoun, Amel Meddeb-Garnaoui
BACKGROUND: We previously identified a Leishmania (L.) major large RAB GTPase (LmlRAB), a new atypical RAB GTPase protein. It is highly conserved in Leishmania species while displaying low level of homology with mammalian homologues. Leishmania small RAB GTPases proteins have been involved in regulation of exocytic and endocytic pathways whereas the role of large RAB GTPases proteins has not been characterized yet. We report here the immunogenicity of both recombinant rLmlRAB and rLmlRABC, in individuals with immunity against L...
April 17, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28415906/effect-of-piplartine-and-cinnamides-on-leishmania-amazonensis-plasmodium-falciparum-and-on-peritoneal-cells-of-swiss-mice
#15
Keline Medeiros de Araújo-Vilges, Stefan Vilges de Oliveira, Shirley Claudino Pereira Couto, Harold Hilarion Fokoue, Gustavo Adolfo Sierra Romero, Massuo Jorge Kato, Luiz Antonio Soares Romeiro, José Roberto Souza Almeida Leite, Selma Aparecida Souza Kuckelhaus
CONTEXT: Plants of the Piperaceae family produce piplartine that was used to synthesize the cinnamides. OBJECTIVE: To assess the effects of piplartine (1) and cinnamides (2-5) against the protozoa responsible for malaria and leishmaniasis, and peritoneal cells of Swiss mice. MATERIALS AND METHODS: Cultures of Leishmania amazonensis, Plasmodium falciparum-infected erythrocytes, and peritoneal cells were incubated, in triplicate, with different concentrations of the compounds (0 to 256 μg/mL)...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28415438/development-of-high-efficacy-peptide-coated-iron-oxide-nanoparticles-encapsulated-amphotericin-b-drug-delivery-system-against-visceral-leishmaniasis
#16
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/28414928/new-iminodibenzyl-derivatives-with-anti-leishmanial-activity
#17
Anderson Arndt, Cleber Wanderlei Liria, Jenicer K U Yokoyama-Yasunaka, M Terêsa Machini, Sílvia Reni Bortolin Uliana, Breno Pannia Espósito
Leishmaniasis is an infection caused by protozoa of the genus Leishmania and transmitted by sandflies. Current treatments are expensive and time-consuming, involving Sb(V)-based compounds, lipossomal amphotericin B and miltefosine. Recent studies suggest that inhibition of trypanothione reductase (TR) could be a specific target in the development of new drugs because it is essential and exclusive to trypanosomatids. This work presents the synthesis and characterization of new iminodibenzyl derivatives (dado) with ethylenediamine (ea), ethanolamine (en) and diethylenetriamine (dien) and their copper(II) complexes...
April 4, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28410591/eurasian-golden-jackal-as-host-of-canine-vector-borne-protists
#18
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/28407812/diagnostic-antigens-for-visceral-leishmaniasis-clarification-of-nomenclatures
#19
REVIEW
Tapan Bhattacharyya, Tegwen Marlais, Michael A Miles
BACKGROUND: Stimulated by the increasing recent use of 'K' or 'rK' nomenclature for antigens reported for visceral leishmaniasis (VL) diagnostic serology, we wished to give a chronological synopsis of their reporting and the potentially confusing terminology. METHODS: The literature was examined for 'K' or 'rK' terminology for VL diagnostic antigens, with emphasis on the original publications in which terms were first used. RESULTS: A chronological account of the first use of these 'K' and 'rK' nomenclatures was compiled...
April 13, 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
#20
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
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