The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform

Gad Baneth - One of the best experts on this subject based on the ideXlab platform.

  • allopurinol resistance in Leishmania infantum from dogs with disease relapse
    PLOS Neglected Tropical Diseases, 2016
    Co-Authors: Daniel Yasurlandau, Charles L Jaffe, Lior David, Gad Baneth
    Abstract:

    Background Visceral Leishmaniasis caused by the protozoan Leishmania infantum is a zoonotic, life threatening parasitic disease. Domestic dogs are the main peridomestic reservoir, and allopurinol is the most frequently used drug for the control of infection, alone or in combination with other drugs. Resistance of Leishmania strains from dogs to allopurinol has not been described before in clinical studies.

  • first report of anaplasma platys infection in red foxes vulpes vulpes and molecular detection of ehrlichia canis and Leishmania infantum in foxes from portugal
    Parasites & Vectors, 2015
    Co-Authors: Luis Cardoso, Matan Gilad, Helder Cortes, Yaarit Nachumbiala, Ana Patricia Lopes, Maria Joao Vilavicosa, Margarida Simoes, Paula Rodrigues, Gad Baneth
    Abstract:

    Background The bacteria Anaplasma platys and Ehrlichia canis and the protozoan Leishmania infantum are vector-borne agents that cause canine vector-borne diseases, some of which are zoonotic. The present survey investigated the prevalence of Anaplasma, Ehrlichia and Leishmania in red foxes (Vulpes vulpes) from Portugal by molecular analysis, in order to evaluate the epidemiological role of these canids as reservoirs of infection.

  • ehrlichia canis and Leishmania infantum co infection a 3 year longitudinal study in naturally exposed dogs
    Clinical Microbiology and Infection, 2009
    Co-Authors: Y Mekuzas, Luigi Gradoni, Gaetano Oliva, Foglia V Manzillo, Gad Baneth
    Abstract:

    Department of Veterinary Clinical Sciences, University Federico II,Naples, ItalyINTRODUCTIONEhrlichiosis and Leishmaniasis are major vector-borne diseases of dogs with a worldwide distri-bution. The causative agents of these diseases,Ehrlichia canis and Leishmania infantum, are intra-cellular pathogens that use monocyte–macrophag-es as host cells. The epidemiology of canineehrlichiosis and Leishmaniasis overlaps in manyareas of the world, because the vector activity andtransmission periods of these pathogens are sim-ilar. Whereas E. canis is transmitted by ticks,mainly Rhipicephalus sanguineus, L. infantum istransmitted by phlebotomine sand flies. Bothinfectious agents disseminate from the skin to thespleen, liver and bone marrow (BM), and activatehost immune mechanisms that induce a range ofimmunopathological responses. The aim of thestudy was to longitudinally evaluate the timecourseandpossiblerelationshipbetweennaturallyoccurring E. canis and L. infantum infections.MATERIALS AND METHODS

  • polymerase chain reaction using noninvasively obtained samples for the detection of Leishmania infantum dna in dogs
    The Journal of Infectious Diseases, 2004
    Co-Authors: Dalit Straussayali, Charles L Jaffe, Ofer Burshtain, Liat Gonen, Gad Baneth
    Abstract:

    A polymerase chain reaction (PCR) procedure using noninvasively obtained samples, for the identification of Leishmania infantum in canine tissues, was evaluated and compared with serologic testing and culture. A total of 92% of naturally infected, symptomatic, seropositive dogs were found to be positive by use of DNA from conjunctival swabs. Spleen or lymph node aspirates were found to be positive by PCR in 86% and by culture in 74% of these dogs. The sensitivity and specificity of conjunctival PCR were 92% and 100%, respectively. Experimentally infected dogs were found to be positive by conjunctival PCR already at 45 days of infection (83%) and before seroconversion. PCR using noninvasively obtained conjunctival samples will be useful for epidemiological studies and for direct diagnosis of canine visceral Leishmaniasis.

María-josé Camarasa - One of the best experts on this subject based on the ideXlab platform.

  • efficient dimerization disruption of Leishmania infantum trypanothione reductase by triazole phenyl thiazoles
    Journal of Medicinal Chemistry, 2021
    Co-Authors: Alejandro Revuelto, Federico Gago, Héctor De ,lucio, María-josé Camarasa, Pedro A Sanchezmurcia, Antonio Jimenezruiz, Juan Carlos Garciasoriano, Sonsoles Velazquez
    Abstract:

    Inhibition of Leishmania infantum trypanothione disulfide reductase (LiTryR) by disruption of its homodimeric interface has proved to be an alternative and unexploited strategy in the search for novel antiLeishmanial agents. Proof of concept was first obtained by peptides and peptidomimetics. Building on previously reported dimerization disruptors containing an imidazole-phenyl-thiazole scaffold, we now report a new 1,2,3-triazole-based chemotype that yields noncompetitive, slow-binding inhibitors of LiTryR. Several compounds bearing (poly)aromatic substituents dramatically improve the ability to disrupt LiTryR dimerization relative to reference imidazoles. Molecular modeling studies identified an almost unexplored hydrophobic region at the interfacial domain as the putative binding site for these compounds. A subsequent structure-based design led to a symmetrical triazole analogue that displayed even more potent inhibitory activity over LiTryR and enhanced leishmanicidal activity. Remarkably, several of these novel triazole-bearing compounds were able to kill both extracellular and intracellular parasites in cell cultures.

  • pyrrolopyrimidine vs imidazole phenyl thiazole scaffolds in nonpeptidic dimerization inhibitors of Leishmania infantum trypanothione reductase
    ACS Infectious Diseases, 2019
    Co-Authors: Alejandro Revuelto, Alejandra A. Carriles, Juan A. Hermoso, Federico Gago, Héctor De ,lucio, Kilian Jesús Gutierrez, Marta Ruizsantaquiteria, Ana Maria Gamo, Pedro A Sanchezmurcia, María-josé Camarasa
    Abstract:

    Disruption of protein–protein interactions of essential oligomeric enzymes by small molecules represents a significant challenge. We recently reported some linear and cyclic peptides derived from an α-helical region present in the homodimeric interface of Leishmania infantum trypanothione reductase (Li-TryR) that showed potent effects on both dimerization and redox activity of this essential enzyme. Here, we describe our first steps toward the design of nonpeptidic small-molecule Li-TryR dimerization disruptors using a proteomimetic approach. The pyrrolopyrimidine and the 5-6-5 imidazole-phenyl-thiazole α-helix-mimetic scaffolds were suitably decorated with substituents that could mimic three key residues (K, Q, and I) of the linear peptide prototype (PKIIQSVGIS-Nle-K-Nle). Extensive optimization of previously described synthetic methodologies was required. A library of 15 compounds bearing different hydrophobic alkyl and aromatic substituents was synthesized. The imidazole-phenyl-thiazole-based analogues...

  • first example of peptides targeting the dimer interface of Leishmania infantum trypanothione reductase with potent in vitro antiLeishmanial activity
    European Journal of Medicinal Chemistry, 2017
    Co-Authors: Marta Ruizsantaquiteria, Federico Gago, Héctor De ,lucio, Kilian Jesús Gutierrez, Pedro A Sanchezmurcia, Miguel A Toro, Sonia De Castro, Filipa A C Carneiro, Antonio Jimenezruiz, María-josé Camarasa
    Abstract:

    Abstract 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. ChemBioChem 2013) 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. Cyclic analogues 3 and 4 were more resistant to proteases than was the linear prototype. Furthermore, the most potent TryR inhibitors in the linear and cyclic series displayed potent in vitro activity against Leishmania infantum upon conjugation with cationic cell-penetrating peptides. To date, these conjugated peptides can be considered the first example of TryR dimerization inhibitors that are active in cell culture.

  • Leishmania infantum endog is an endo exo nuclease essential for parasite survival
    PLOS ONE, 2014
    Co-Authors: Eva Rico, Cristina Oliva, Kilian Jesús Gutierrez, Juan F. Alzate, Carlos Mario Genes, David Moreno, Elena Casanova, Alba Gigante, Mariajesus Perezperez, María-josé Camarasa
    Abstract:

    EndoG, a member of the DNA/RNA non-specific ββα-metal family of nucleases, has been demonstrated to be present in many organisms, including Trypanosomatids. This nuclease participates in the apoptotic program in these parasites by migrating from the mitochondrion to the nucleus, where it takes part in the degradation of genomic DNA that characterizes this process. We now demonstrate that Leishmania infantum EndoG (LiEndoG) is an endo-exonuclease that has a preferential 5′ exonuclease activity on linear DNA. Regardless of its role during apoptotic cell death, this enzyme seems to be necessary during normal development of the parasites as indicated by the reduced growth rates observed in LiEndoG hemi-knockouts and their poor infectivity in differentiated THP-1 cells. The pro-life role of this protein is also corroborated by the higher survival rates of parasites that over-express this protein after treatment with the LiEndoG inhibitor Lei49. Taken together, our results demonstrate that this enzyme plays essential roles in both survival and death of Leishmania parasites.

Michele Trotta - One of the best experts on this subject based on the ideXlab platform.

Eduardo De Almeida Marquesdasilva - One of the best experts on this subject based on the ideXlab platform.

Thaís Viana Fialho Martins - One of the best experts on this subject based on the ideXlab platform.