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leishmania parasites

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https://www.readbyqxmd.com/read/29777624/characterisation-of-a-putative-glutamate-5-kinase-from-leishmania-donovani
#1
Natasha Sienkiewicz, Han B Ong, Alan H Fairlamb
Previous metabolic studies have demonstrated that leishmania parasites are able to synthesise proline from glutamic acid and threonine from aspartic acid. The first committed step in both biosynthetic pathways involves an amino acid kinase, either a glutamate 5-kinase (EC 2.7.2.11) or an aspartokinase (EC 2.7.2.4). Bioinformatic analysis of multiple leishmania genomes identifies a single amino-acid-kinase gene (LdBPK 262740.1) variously annotated as either a putative glutamate or aspartate kinase. To establish the catalytic function of this Leishmania donovani gene product, we have determined the physical and kinetic properties of the recombinant enzyme purified from Escherichia coli...
May 19, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29775225/cytokines-and-chemokines-differentially-regulate-innate-immune-cell-trafficking-during-post-kala-azar-dermal-leishmaniasis
#2
Ashish K Singh, Vidya N R Das, Ajay Amit, Manas R Dikhit, Vijaya Mahantesh, Shubhankar K Singh, Shyam Naryan, Krishna Pandey, Pradeep Das, Neena Verma, Sanjiva Bimal
Post kala-azar dermal leishmaniasis (PKDL) is often considered to be the anthroponotic reservoir of visceral leishmaniasis (VL) in India. A better understanding of the host immune-response in dermal lesions of PKDL patients is therefore of utmost significance to minimize such patients and to restrict VL transmission. Although the innate immune response is known to play an important role in parasite clearance from dermal lesions, the actual contribution of innate cells to the pathogenicity of PKDL is poorly understood...
May 18, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29774958/effect-of-trapping-method-on-species-identification-of-phlebotomine-sandflies-by-maldi-tof-ms-protein-profiling
#3
P Halada, K Hlavackova, J Risueño, E Berriatua, P Volf, V Dvorak
Sandflies (Diptera: Psychodidae) (Newstead, 1911) are blood-feeding insects that transmit human pathogens including Leishmania (Trypanosomatida: Trypanosomatidae) parasites, causative agents of the leishmaniases. To elucidate Leishmania transmission cycles, conclusive identification of vector species is essential. Molecular approaches including matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) protein profiling have recently emerged to complement morphological identification...
May 18, 2018: Medical and Veterinary Entomology
https://www.readbyqxmd.com/read/29773132/leishmania-in-wolves-in-northern-spain-a-spreading-zoonosis-evidenced-by-wildlife-sanitary-surveillance
#4
Alvaro Oleaga, Stefania Zanet, Alberto Espí, Marcia Raquel Pegoraro de Macedo, Christian Gortázar, Ezio Ferroglio
Leishmaniosis is, to date, considered the second most important emerging vector-borne protozoal disease in the world after malaria. The form of zoonotic visceral leishmaniosis found in the Mediterranean basin is caused by Leishmania infantum, and its life cycle includes the domestic dog and a phlebotomine sandfly vector. This complex epidemiological cycle and its high prevalence of subclinical infection, hinder the surveillance and control of L. infantum, and allows it to go unnoticed at the geographical endemicity limits of the parasite or in recently colonized areas...
May 15, 2018: Veterinary Parasitology
https://www.readbyqxmd.com/read/29773051/dna-topoisomerases-of-leishmania-parasites-druggable-targets-for-drug-discovery
#5
Rosa Mª Reguer, Ehab Kotb Elmahallaw, Carlos Garcia-Estrada, Ruben Carbajo-Andres, Rafael Balana-Fouce
DNA topoisomerases (Top) are a group of isomerase enzymes responsible for controlling the topological problems caused by DNA double helix in the cell during the processes of replication, transcription and recombination. Interestingly, these enzymes have been known since long to be key molecular machines in several cellular processes through overwinding or underwinding of DNA in all-living organisms. Leishmania, a trypanosomatid parasite responsible for causing fatal diseases mostly in impoverished populations of low-income countries, have a set of six classes of Top enzymes...
May 17, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29772025/shape-shifting-trypanosomes-flagellar-shortening-followed-by-asymmetric-division-in-trypanosoma-congolense-from-the-tsetse-proventriculus
#6
Lori Peacock, Christopher Kay, Mick Bailey, Wendy Gibson
Trypanosomatids such as Leishmania and Trypanosoma are digenetic, single-celled, parasitic flagellates that undergo complex life cycles involving morphological and metabolic changes to fit them for survival in different environments within their mammalian and insect hosts. According to current consensus, asymmetric division enables trypanosomatids to achieve the major morphological rearrangements associated with transition between developmental stages. Contrary to this view, here we show that the African trypanosome Trypanosoma congolense, an important livestock pathogen, undergoes extensive cell remodelling, involving shortening of the cell body and flagellum, during its transition from free-swimming proventricular forms to attached epimastigotes in vitro...
May 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29768103/efficacy-of-recombinase-polymerase-amplification-to-diagnose-trypanosoma-cruzi-infection-in-dogs-with-cardiac-alterations-from-an-endemic-area-of-mexico
#7
Matilde Jimenez-Coello, Thomas Shelite, Alejandro Castellanos-Gonzalez, Omar Saldarriaga, Rocio Rivero, Antonio Ortega-Pacheco, Carlos Acevedo-Arcique, Karla Amaya-Guardia, Nisha Garg, Peter Melby, Bruno L Travi
Chagas disease is a lingering Public Health problem in Latin America with ∼5.7 million people infected with Trypanosoma cruzi. Transmission is still taking place in most countries of the Americas, including the United States. Dogs are frequently infected with T. cruzi and its high infection prevalence is associated with increased risk of Chagas disease in humans. The city of Mérida in the Yucatan peninsula is endemic for Chagas disease and canines are frequently infected with T. cruzi. The objective of this study was to evaluate the performance of a qualitative point of care (POC) molecular test (RPA-LF, recombinase polymerase amplification-lateral flow) developed in our laboratory for identifying infected dogs...
May 16, 2018: Vector Borne and Zoonotic Diseases
https://www.readbyqxmd.com/read/29765675/-leishmania-naiffi-and-leishmania-guyanensis-reference-genomes-highlight-genome-structure-and-gene-evolution-in-the-viannia-subgenus
#8
Simone Coughlan, Ali Shirley Taylor, Eoghan Feane, Mandy Sanders, Gabriele Schonian, James A Cotton, Tim Downing
The unicellular protozoan parasite Leishmania causes the neglected tropical disease leishmaniasis, affecting 12 million people in 98 countries. In South America, where the Viannia subgenus predominates, so far only L. ( Viannia ) braziliensis and L. ( V. ) panamensis have been sequenced, assembled and annotated as reference genomes. Addressing this deficit in molecular information can inform species typing, epidemiological monitoring and clinical treatment. Here, L. ( V. ) naiffi and L. ( V. ) guyanensis genomic DNA was sequenced to assemble these two genomes as draft references from short sequence reads...
April 2018: Royal Society Open Science
https://www.readbyqxmd.com/read/29758517/identification-of-chalcone-based-antileishmanial-agents-targeting-trypanothione-reductase
#9
Margherita Ortalli, Andrea Ilari, Gianni Colotti, Ilenia De Ionna, Theo Battista, Alessandra Bisi, Silvia Gobbi, Angela Rampa, Rita M C Di Martino, Giovanna A Gentilomi, Stefania Varani, Federica Belluti
All currently used first-line and second-line drugs for the treatment of leishmaniasis exhibit several drawbacks including toxicity, high costs and route of administration. Furthermore, some drugs are associated with the emergence of drug resistance. Thus, the development of new treatments for leishmaniasis is a priority in the field of neglected tropical diseases. The present work highlights the use of natural derived products, i.e. chalcones, as potential source of antileishmanial agents. Thirty-one novel chalcone compounds have been synthesized and their activity has been evaluated against promastigotes of Leishmania donovani; 16 compounds resulted active against L...
May 2, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29757380/simultaneous-population-pharmacokinetic-modelling-of-plasma-and-intracellular-pbmc-miltefosine-concentrations-in-new-world-cutaneous-leishmaniasis-and-exploration-of-exposure-response-relationships
#10
Anke E Kip, María Del Mar Castro, Maria Adelaida Gomez, Alexandra Cossio, Jan H M Schellens, Jos H Beijnen, Nancy Gore Saravia, Thomas P C Dorlo
Objectives: Leishmania parasites reside within macrophages and the direct target of antileishmanial drugs is therefore intracellular. We aimed to characterize the intracellular PBMC miltefosine kinetics by developing a population pharmacokinetic (PK) model simultaneously describing plasma and intracellular PBMC pharmacokinetics. Furthermore, we explored exposure-response relationships and simulated alternative dosing regimens. Patients and methods: A population PK model was developed with NONMEM, based on 339 plasma and 194 PBMC miltefosine concentrations from Colombian cutaneous leishmaniasis patients [29 children (2-12 years old) and 22 adults] receiving 1...
May 10, 2018: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29757339/novel-antimony-iii-hydroxamic-acid-complexes-as-potential-anti-leishmanial-agents
#11
D M Keogan, S S C Oliveira, L S Sangenito, M H Branquinha, R D Jagoo, B Twamley, A L S Santos, D M Griffith
Reaction of benzohydroxamic acid (Bha), 2-pyridinehydroxamic acid (2-pyha), 2-amino-phenylhydroxamic acid (2-NH2-pha) and salicylhydroxamic acid (Sha) with SbCl3 in ethanol gave the corresponding novel hydroxamato Sb(iii) complexes, [Sb(Bha-1H)2Cl] 1, [SbCl2(2-pyha-1H)] 2, [Sb(2-NH2-pha-1H)(2-NH3-pha-1H)]Cl2 3 and [SbCl(Sha-1H)2] 4. In all cases the hydroxamic acids coordinate to the Sb centres in the typical bidentate hydroxamato (O,O') coordination mode, via the carbonyl oxygen and deprotonated hydroxyl group...
May 14, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/29751117/cell-death-mechanisms-in-leishmania-amazonensis-triggered-by-methylene-blue-mediated-antiparasitic-photodynamic-therapy
#12
Débora P Aureliano, José Angelo Lauletta Lindoso, Sandra Regina de Castro Soares, Cleusa Fumika Hirata Takakura, Thiago Martini Pereira, Martha Simões Ribeiro
Antiparasitic photodynamic therapy (ApPDT) is an emerging approach to manage cutaneous leishmaniasis (CL) since no side effects, contraindications and parasite resistance have been reported. In addition, methylene blue (MB) is a suitable photosensitizer to mediate ApPDT on CL. In this study we aimed to look for the best parameters to eradicate Leishmania amazonensis and investigated the cell death pathways involved in MB-mediated ApPDT. MB uptake by parasites was determined using different MB concentrations (50, 100, 250 and 500 μM) and incubation times (10, 30 and 60 min)...
May 8, 2018: Photodiagnosis and Photodynamic Therapy
https://www.readbyqxmd.com/read/29749562/medicinal-fungi-a-source-of-antiparasitic-secondary-metabolites
#13
REVIEW
Juliana Lenzi, Tania Maria Costa, Michele Debiasi Alberton, Juliane Araújo Greinert Goulart, Lorena Benathar Ballod Tavares
Regions with a tropical climate are frequently affected by endemic diseases caused by pathogenic parasites. More than one billion people worldwide are exposed directly to tropical parasites. The literature cites several antiparasitic metabolites obtained from medicinal plants or via synthetic pathways. However, fungi produce a diversity of metabolites that play important biological roles in human well-being. Thus, they are considered a potential source of novel natural agents for exploitation in the pharmaceutical industry...
May 10, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29747123/hiv-aspartyl-protease-inhibitors-modify-the-percentage-of-activated-leukocytes-as-well-as-serum-levels-of-il-17a-and-no-during-experimental-leishmaniasis
#14
Daniele Luísa Ribeiro Alvarenga, Amanda Helen Dos Santos Silva, Jacqueline Araújo Fiuza, Soraya Torres Gaze, Jaquelline Germano de Oliveira, Rodrigo Corrêa Oliveira, Carlos Eduardo Calzavara-Silva, Marcelo Antônio Pascoal-Xavier, Érica Alessandra Rocha Alves
HIV aspartyl protease inhibitors are able to modulate multiple defense mechanisms. However, their influence on the immune response against Leishmania has rarely been investigated. The aim of our study was to investigate whether in vivo treatment with HIV aspartyl protease inhibitors is able to modulate the immune response during Leishmania infection. Using Leishmania (L.) amazonensis-infected mice, we analyzed the disease evolution and parasite load, immunophenotypic profiles of splenic T and B lymphocytes, numbers of lymphoid aggregates in the spleen, percentages of circulating atypical lymphocytes and reactive monocytes, and serum levels of cytokines and nitric oxide (NO) after 30 days of oral treatment with lopinavir/ritonavir (LPV/RTV) or atazanavir (ATV)...
May 7, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29746872/the-contribution-of-the-dna-microarray-technology-to-gene-expression-profiling-in-leishmania-spp-a-retrospective
#15
REVIEW
Ana Alonso, Vicente Larraga, Pedro J Alcolea
The first genome project of any living organism excluding viruses, the gammaproteobacteria Haemophilus influenzae, was completed in 1995. Until the last decade, genome sequencing was very tedious because genome survey sequences (GSS) and/or expressed sequence tags (ESTs) belonging to plasmid, cosmid and artificial chromosome genome libraries had to be sequenced and assembled in silico. Nowadays, no genome is completely assembled actually, because gaps and unassembled contigs are always remaining. However, most represent the whole genome of the organism of origin from a practical point of view...
May 7, 2018: Acta Tropica
https://www.readbyqxmd.com/read/29745990/an-il-10-dominant-polarization-of-monocytes-is-a-feature-of-indian-visceral-leishmaniasis
#16
Susmita Roy, Debanjan Mukhopadhyay, Shibabrata Mukherjee, Srija Moulik, Soumyadip Chatterji, Nayan Brahme, Netai Pramanik, Rama P Goswami, Bibhuti Saha, Mitali Chatterjee
BACKGROUND: Leishmania donovani, the causative parasite of Visceral Leishmaniasis (VL) deviously manipulates host monocytes/macrophages to ensure its survival. Although monocytes/macrophages from patients with VL have demonstrated an impaired oxidative burst and antigen presentation, an unanswered yet pertinent question remains as to whether they are deactivated or alternatively activated. METHODS AND RESULTS: The significantly raised plasma levels of IL-4/IL-13 and IL-10 in VL patients suggested a microenvironment conducive for alternative activation of monocytes/macrophages...
May 10, 2018: Parasite Immunology
https://www.readbyqxmd.com/read/29744736/compounds-from-african-medicinal-plants-with-activities-against-selected-parasitic-diseases-schistosomiasis-trypanosomiasis-and-leishmaniasis
#17
REVIEW
Conrad V Simoben, Fidele Ntie-Kang, Sergi H Akone, Wolfgang Sippl
Parasitic diseases continue to represent a threat on a global scale, particularly among the poorest countries in the world. This is particularly because of the absence of vaccines, and in some cases, resistance against available drugs, currently being used for their treatment. In this review emphasis is laid on natural products and scaffolds from African medicinal plants (AMPs) for lead drug discovery and possible further development of drugs for the treatment of parasitic diseases. In the discussion, emphasis has been laid on alkaloids, terpenoids, quinones, flavonoids and narrower compound classes of compounds with micromolar range activities against Schistosoma, Trypanosoma and Leishmania species...
May 9, 2018: Natural Products and Bioprospecting
https://www.readbyqxmd.com/read/29743809/evaluation-of-regulatory-immune-response-in-skin-lesions-of-patients-affected-by-nonulcerated-or-atypical-cutaneous-leishmaniasis-in-honduras-central-america
#18
Gabriela Venicia Araujo Flores, Carmen Maria Sandoval Pacheco, Thaise Yumie Tomokane, Wilfredo Sosa Ochoa, Concepción Zúniga Valeriano, Claudia Maria Castro Gomes, Carlos Eduardo Pereira Corbett, Marcia Dalastra Laurenti
In Honduras, Leishmania (L.) infantum chagasi causes both visceral leishmaniasis (LV) and nonulcerated or atypical cutaneous leishmaniasis (NUCL). NUCL is characterized by mononuclear inflammatory infiltration of the dermis, composed mainly of lymphocytes followed by macrophages with discrete parasitism. Considering that little is known about the pathogenesis of NUCL, the aim of this study was to evaluate the regulatory response in situ in skin lesions of patients affected by NUCL. Biopsies ( n = 20) from human cutaneous nonulcerative lesions were collected and processed by usual histological techniques...
2018: Mediators of Inflammation
https://www.readbyqxmd.com/read/29740532/epidemiological-aspects-of-visceral-leishmaniasis-in-larestan-and-ghiro-karzin-counties-southwest-of-iran
#19
Nasiri Zahra, Keshavarzi Davood, Akbari Morteza, Soltani Zahra
Objectives: Leishmania parasites are the causative agents of leishmaniasis. The Visceral leishmaniasis (VL) form of the disease is fatal if not treated in most cases. This study examined the epidemiological aspects of VL in two southwest counties of Iran. Methods: This was a retrospective study of hospitalized patients with a laboratory confirmation of VL from Larestan and Ghiro-Karzin Counties. Results: For Larestan county, a decline in the incidence of VL has been observed from 2004 to 2015...
April 2018: Osong Public Health and Research Perspectives
https://www.readbyqxmd.com/read/29740446/antigenicity-of-leishmania-activated-c-kinase-antigen-lack-in-human-peripheral-blood-mononuclear-cells-and-protective-effect-of-prime-boost-vaccination-with-pci-neo-lack-plus-attenuated-lack-expressing-vaccinia-viruses-in-hamsters
#20
Laura Fernández, Eugenia Carrillo, Lucas Sánchez-Sampedro, Carmen Sánchez, Ana Victoria Ibarra-Meneses, M Angeles Jimenez, Valter Dos Anjos Almeida, Mariano Esteban, Javier Moreno
Leishmania -activated C-kinase antigen (LACK) is a highly conserved protein among Leishmania species and is considered a viable vaccine candidate for human leishmaniasis. In animal models, prime-boost vaccination with LACK-expressing plasmids plus attenuated vaccinia viruses (modified vaccinia Ankara [MVA] and mutant M65) expressing LACK, has been shown to protect against cutaneous leishmaniasis (CL). Further, LACK demonstrated to induce the production of protective cytokines in patients with active CL or cured visceral leishmaniasis, as well as in asymptomatic individuals from endemic areas...
2018: Frontiers in Immunology
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