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Camila Oliveira, Paulo Costa Carvalho, Lysangela Ronalte Alves, Samuel Goldenberg
The regulation of gene expression in trypanosomatids occurs mainly at the post-transcriptional level. Despite the importance of this type of control in Trypanosoma cruzi, few RNA binding proteins have been characterized. The RRM domain (RNA Recognition Motif) is one of the most abundant domains found in RNA-binding proteins in higher eukaryotes. Proteins containing the RRM domain are involved in the majority of post-transcriptional processes regulating gene expression. In this work, we aimed to characterize the protein TcNRBD1 from T...
2016: PloS One
Juan Felipe Osorio-Méndez, Andrea Vizcaíno-Castillo, Rebeca Manning-Cela, Roberto Hernandez, Ana María Cevallos
The role and regulation of actin in Trypanosoma cruzi and other related parasites is largely unknown. Based on early genome analysis, it was proposed that there was a reduced dependency on the acto-myosin system in the trypanosomatid parasites. However, more recent studies have extended the set of potential actin regulatory proteins, particularly for T. cruzi. One of the identified actin-binding proteins in trypanosomatids is profilin. In other systems, it is capable of simultaneously binding both monomeric actin and several actin-regulatory factors...
October 15, 2016: Biochemical and Biophysical Research Communications
Magdalena Jancarova, Jana Hlavacova, Jan Votypka, Petr Volf
BACKGROUND: In mosquitoes, it has previously been shown that rearing conditions of immature stages have an effect on the vector competence of adults. Here, we studied the impact of different larval rearing temperatures (27 °C versus 32 °C) on the sand fly Phlebotomus sergenti Parrot, 1917 and its susceptibility to two parasites: Leishmania tropica Wright, 1903, a dixenous trypanosomatid transmissible from sand flies to humans, and Psychodiella sergenti Lantova, Volf & Votypka, 2010, a monoxenous sand fly gregarine...
October 18, 2016: Parasites & Vectors
Atchara Phumee, Apiwat Tawatsin, Usavadee Thavara, Theerakamol Pengsakul, Suwich Thammapalo, Jérôme Depaquit, Frédérick Gay, Padet Siriyasatien
Although female sand flies are best known as the vectors of Leishmania parasites and viruses, several previous reports have demonstrated that these insects can also act as vectors for the trypanosomes of bats, lizards, and snakes. In this report, we created an inventory of Phlebotomine sand flies from southern Thailand. A novel trypanosome was found in a specimen of Phlebotomus stantoni, and two sand fly species newly recorded in the country, Sergentomyia khawi and Sergentomyia hivernus, were described. PCR primer pairs specific for the internal transcribed spacer 1 (ITS1) and the small subunit ribosomal DNA (SSU rDNA) gene of trypanosomatids were used to demonstrate the presence of the parasite in the sand fly...
October 15, 2016: Journal of Medical Entomology
Cher-Pheng Ooi, Sarah Schuster, Christelle Cren-Travaillé, Eloise Bertiaux, Alain Cosson, Sophie Goyard, Sylvie Perrot, Brice Rotureau
Trypanosoma vivax is the most prevalent trypanosome species in African cattle. It is thought to be transmitted by tsetse flies after cyclical development restricted to the vector mouthparts. Here, we investigated the kinetics of T. vivax development in Glossina morsitans morsitans by serial dissections over 1 week to reveal differentiation and proliferation stages. After 3 days, stable numbers of attached epimastigotes were seen proliferating by symmetric division in the cibarium and proboscis, consistent with colonization and maintenance of a parasite population for the remaining lifespan of the tsetse fly...
2016: Frontiers in Cellular and Infection Microbiology
Jose A Garcia-Salcedo, Juan D Unciti-Broceta, Javier Valverde-Pozo, Miguel Soriano
Leishmania and Trypanosoma are members of the Trypanosomatidae family that cause severe human infections such as leishmaniasis, Chagas disease, and sleeping sickness affecting millions of people worldwide. Despite efforts to eradicate them, migrations are expanding these infections to developing countries. There are no vaccines available and current treatments depend only on chemotherapy. Drug resistance is a major obstacle for the treatment of these diseases given that existing drugs are old and limited, with some having severe side effects...
2016: Frontiers in Pharmacology
Sanofar Abdeen, Nilshad Salim, Najiba Mammadova, Corey M Summers, Karen Goldsmith-Pestana, Diane McMahon-Pratt, Peter G Schultz, Arthur L Horwich, Eli Chapman, Steven M Johnson
Trypanosoma brucei are protozoan parasites that cause African sleeping sickness in humans (also known as Human African Trypanosomiasis-HAT). Without treatment, T. brucei infections are fatal. There is an urgent need for new therapeutic strategies as current drugs are toxic, have complex treatment regimens, and are becoming less effective owing to rising antibiotic resistance in parasites. We hypothesize that targeting the HSP60/10 chaperonin systems in T. brucei is a viable anti-trypanosomal strategy as parasites rely on these stress response elements for their development and survival...
September 22, 2016: Bioorganic & Medicinal Chemistry Letters
Luciana Loureiro Penha, Luísa Hoffmann, Silvanna Sant'Anna de Souza, Allan Cézar de Azevedo Martins, Thayane Bottaro, Francisco Prosdocimi, Débora Souza Faffe, Maria Cristina Machado Motta, Turán Péter Ürményi, Rosane Silva
Trypanosomatids are parasites that cause disease in humans, animals, and plants. Most are non-pathogenic and some harbor a symbiotic bacterium. Endosymbiosis is part of the evolutionary process of vital cell functions such as respiration and photosynthesis. Angomonas deanei is an example of a symbiont-containing trypanosomatid. In this paper, we sought to investigate how symbionts influence host cells by characterising and comparing the transcriptomes of the symbiont-containing A. deanei (wild type) and the symbiont-free aposymbiotic strains...
October 3, 2016: Memórias do Instituto Oswaldo Cruz
Eva Iniguez, Armando Varela-Ramirez, Alberto Martínez, Caresse L Torres, Roberto A Sánchez-Delgado, Rosa A Maldonado
In previous studies we reported a novel series of organometallic compounds, Ru(II) complexed with clotrimazole, displaying potent trypanosomatid activity with unnoticeable toxicity toward normal mammalian cells. In view of the promising activity of Ru-clotrimazole complexes against Leishmania major (L. major), the present work sought to investigate the anti-leishmanial activity of the AM162 complex in the murine model of cutaneous leishmaniasis. In addition, to facilitate the design of new therapeutic strategies against this disease, we investigated the mode of action of two Ru-clotrimazole complexes in L...
September 30, 2016: Acta Tropica
C C Avila, F G Almeida, G Palmisano
Accurate and rapid determination of trypanosomatids is essential in epidemiological surveillance and therapeutic studies. Matrix-assisted laser desorption ionization/time of flight mass spectrometry (MALDI-TOF MS) has been shown to be a useful and powerful technique to identify bacteria, fungi, metazoa and human intact cells with applications in clinical settings. Here, we developed and optimized a MALDI-TOF MS method to profile trypanosomatids. trypanosomatid cells were deposited on a MALDI target plate followed by addition of matrix solution...
August 2016: Journal of Mass Spectrometry: JMS
Luke Maishman, Samson O Obado, Sam Alsford, Jean-Mathieu Bart, Wei-Ming Chen, Alexander V Ratushny, Miguel Navarro, David Horn, John D Aitchison, Brian T Chait, Michael P Rout, Mark C Field
The nuclear lamina is a filamentous structure subtending the nuclear envelope and required for chromatin organization, transcriptional regulation and maintaining nuclear structure. The trypanosomatid coiled-coil NUP-1 protein is a lamina component functionally analogous to lamins, the major lamina proteins of metazoa. There is little evidence for shared ancestry, suggesting the presence of a distinct lamina system in trypanosomes. To find additional trypanosomatid lamina components we identified NUP-1 interacting proteins by affinity capture and mass-spectrometry...
September 12, 2016: Nucleic Acids Research
Jader Santos Cruz, Fabiana Simão Machado, Catherine Ropert, Danilo Roman-Campos
Chagas disease is caused by the trypanosomatid Trypanosoma cruzi, which chronically causes heart problems in up to 30% of infected patients. Chagas disease was initially restricted to Latin America. However, due to migratory events, this disease may become a serious worldwide health problem. During Chagas disease, many patients die of cardiac arrhythmia despite the apparent benefits of anti-arrhythmic therapy (e.g., amiodarone). Here, we assimilate the cardiac form of Chagas disease to an inflammatory cardiac disease...
August 11, 2016: Trends in Cardiovascular Medicine
Mariela Florencia Martínez, Martín Miguel Kowalewski, Oscar Daniel Salomón, Alejandro Gabriel Schijman
The transmission of Trypanosoma cruzi by vectors is confined to the Americas, and the infection circulates in at least two broadly defined transmission cycles occurring in domestic and sylvatic habitats. This study sought to detect and characterize infection by T. cruzi and other trypanosomes using PCR strategies in blood samples from free-ranging howler monkeys, Alouatta caraya, in the northeastern Argentina. Blood samples were collected at four sites with variable levels of habitat modification by human activity...
August 2016: International Journal for Parasitology. Parasites and Wildlife
Martin Zoltner, David Horn, Harry P de Koning, Mark C Field
Pathogenic protozoa are evolutionarily highly divergent from their metazoan hosts, reflected in many aspects of their biology. One particularly important parasite taxon is the trypanosomatids. Multiple transmission modes, distinct life cycles and exploitation of many host species attests to great prowess as parasites, and adaptability for efficient, chronic infection. Genome sequencing has begun uncovering how trypanosomatids are well suited to parasitism, and recent genetic screening and cell biology are revealing new aspects of how to control these organisms and prevent disease...
September 9, 2016: Current Opinion in Microbiology
Kristína Záhonová, Alexei Y Kostygov, Tereza Ševčíková, Vyacheslav Yurchenko, Marek Eliáš
A limited number of non-canonical genetic codes have been described in eukaryotic nuclear genomes. Most involve reassignment of one or two termination codons as sense ones [1-4], but no code variant is known that would have reassigned all three termination codons. Here, we describe such a variant that we discovered in a clade of trypanosomatids comprising nominal Blastocrithidia species. In these protists, UGA has been reassigned to encode tryptophan, while UAG and UAA (UAR) have become glutamate encoding. Strikingly, UAA and, less frequently, UAG also serve as bona fide termination codons...
September 12, 2016: Current Biology: CB
Leonardo M Fonseca, Tatiana C Garcez, Luciana Penha, Leonardo Freire-DE-Lima, Emmanuel Maes, Kelli M Costa, Lucia Mendonça-Previato, Jose O Previato
One of the main obstacles to the treatment of Chagas disease is the genetic and phenotypical variance displayed by T. cruzi strains, resulting in differences in morphology, virulence, pathogenicity and drug susceptibility. To better understand the role of glycoconjungates in Chagas disease, we performed the molecular characterization of the O-linked chains from mucins and glycoinositolphospholipids (GIPLs) of the Silvio X10 clone 1 strain. We demonstrated the presence of a β-galactofuranose (β-Galf) unity linked to the O-4 position of the α-N-acetylglucosamine (α-GlcNAc)O-4 in Tc-mucins...
September 2016: Anais da Academia Brasileira de Ciências
C M Genes, H de Lucio, V M González, P A Sánchez-Murcia, E Rico, F Gago, N Fasel, A Jiménez-Ruiz
Despite the absence of sequences showing significant similarity to any of the members of the Bcl-2 family of proteins in protozoa, experiments carried out in yeast or trypanosomatids have demonstrated that ectopic expression of some of these members alters their response to different death stimuli. Because the BH3 domain is the smallest common signature in all the proteins of this family of apoptosis regulators and also because they are essential for molecular interactions between antagonistic members, we looked for sequences with significant similarity to the BH3 motif in the Leishmania infantum genome...
2016: Cell Death Discovery
Anita Leocadio Freitas-Mesquita, Marta T Gomes, Danielle P Vieira, Lisvane Paes-Vieira, Michelle T C Nascimento, Angela H C S Lopes, José Roberto Meyer-Fernandes
The protozoan parasite Leishmania amazonensis is the etiological agent of cutaneous leishmaniasis. During its life cycle, the flagellated metacyclic promastigote forms are transmitted to vertebrate hosts by sandfly bites, and they develop into amastigotes inside macrophages, where they multiply. L. amazonensis possesses a bifunctional enzyme, called 3'-nucleotidase/nuclease (3'NT/NU), which is able to hydrolyze extracellular 3'-monophosphorylated nucleosides and nucleic acids. 3'NT/NU plays an important role in the generation of extracellular adenosine and has been described as a key enzyme in the acquisition of purines by trypanosomatids...
October 2016: Experimental Parasitology
Ligia Cristina Kalb, Yohana Camila A Frederico, Cordula Boehm, Claudia Maria do Nascimento Moreira, Maurilio José Soares, Mark C Field
Trypanosomatids are parasitic protozoa with a significant burden on human health. African and American trypanosomes are causative agents of Nagana and Chagas disease respectively, and speciated about 300 million years ago. These parasites have highly distinct life cycles, pathologies, transmission strategies and surface proteomes, being dominated by the variant surface glycoprotein (African) or mucins (American) respectively. In African trypanosomes clathrin-mediated trafficking is responsible for endocytosis and post-Golgi transport, with several mechanistic aspects distinct from higher organisms...
2016: Scientific Reports
Silvia Desy, Jan Mani, Anke Harsman, Sandro Käser, André Schneider
TbLOK1 has previously been characterized as a trypanosomatid-specific mitochondrial outer membrane protein whose ablation caused a collapse of the mitochondrial network, disruption of the membrane potential and loss of mitochondrial DNA. Here we show that ablation of TbLOK1 primarily abolishes mitochondrial protein import, both in vivo and in vitro. Co-immunprecipitations together with blue native gel analysis demonstrate that TbLOK1 is a stable and stoichiometric component of the archaic protein translocase of the outer membrane (ATOM), the highly diverged functional analogue of the TOM complex in other organisms...
November 2016: Molecular Microbiology
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