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https://www.readbyqxmd.com/read/28344657/well-positioned-nucleosomes-punctuate-polycistronic-pol-ii-transcription-units-and-flank-silent-vsg-gene-arrays-in-trypanosoma-brucei
#1
Johannes Petrus Maree, Megan Lindsay Povelones, David Johannes Clark, Gloria Rudenko, Hugh-George Patterton
BACKGROUND: The compaction of DNA in chromatin in eukaryotes allowed the expansion of genome size and coincided with significant evolutionary diversification. However, chromatin generally represses DNA function, and mechanisms coevolved to regulate chromatin structure and its impact on DNA. This included the selection of specific nucleosome positions to modulate accessibility to the DNA molecule. Trypanosoma brucei, a member of the Excavates supergroup, falls in an ancient evolutionary branch of eukaryotes and provides valuable insight into the organization of chromatin in early genomes...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28338335/stress-induced-protein-s-glutathionylation-and-s-trypanothionylation-in-african-trypanosomes-a-quantitative-redox-proteome-and-thiol-analysis
#2
Kathrin Ulrich, Caroline Finkenzeller, Sabine Merker, Federico Rojas, Keith Matthews, Thomas Ruppert, R Luise Krauth-Siegel
AIMS: Trypanosomatids have a unique trypanothione-based thiol redox metabolism. The parasite-specific dithiol is synthesized from glutathione and spermidine, with glutathionylspermidine as intermediate catalyzed by trypanothione synthetase. In this study, we address the oxidative stress response of African trypanosomes with special focus on putative protein S-thiolation. RESULTS: Challenging bloodstream Trypanosoma brucei with diamide, H2O2 or hypochlorite results in distinct levels of reversible overall protein S-thiolation...
March 24, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28334017/genome-wide-rnai-selection-identifies-a-regulator-of-transmission-stage-enriched-gene-families-and-cell-type-differentiation-in-trypanosoma-brucei
#3
Eva Rico, Alasdair Ivens, Lucy Glover, David Horn, Keith R Matthews
Trypanosoma brucei, causing African sleeping-sickness, exploits quorum-sensing (QS) to generate the 'stumpy forms' necessary for the parasite's transmission to tsetse-flies. These quiescent cells are generated by differentiation in the bloodstream from proliferative slender forms. Using genome-wide RNAi selection we screened for repressors of transmission stage-enriched mRNAs in slender forms, using the stumpy-elevated ESAG9 transcript as a model. This identified REG9.1, whose RNAi-silencing alleviated ESAG9 repression in slender forms and tsetse-midgut procyclic forms...
March 23, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28331592/host-sharing-by-the-honey-bee-parasites-lotmaria-passim-and-nosema-ceranae
#4
Manuel Tritschler, Gina Retschnig, Orlando Yañez, Geoffrey R Williams, Peter Neumann
The trypanosome Lotmaria passim and the microsporidian Nosema ceranae are common parasites of the honey bee, Apis mellifera, intestine, but the nature of interactions between them is unknown. Here, we took advantage of naturally occurring infections and quantified infection loads of individual workers (N = 408) originating from three apiaries (four colonies per apiary) using PCR to test for interactions between these two parasites. For that purpose, we measured the frequency of single and double infections, estimated the parasite loads of single and double infections, and determined the type of correlation between both parasites in double infections...
March 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/28331591/synergistic-effects-of-floral-phytochemicals-against-a-bumble%C3%A2-bee-parasite
#5
Evan C Palmer-Young, Ben M Sadd, Rebecca E Irwin, Lynn S Adler
Floral landscapes comprise diverse phytochemical combinations. Individual phytochemicals in floral nectar and pollen can reduce infection in bees and directly inhibit trypanosome parasites. However, gut parasites of generalist pollinators, which consume nectar and pollen from many plant species, are exposed to phytochemical combinations. Interactions between phytochemicals could augment or decrease effects of single compounds on parasites. Using a matrix of 36 phytochemical treatment combinations, we assessed the combined effects of two floral phytochemicals, eugenol and thymol, against four strains of the bumblebee gut trypanosome Crithidia bombi...
March 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/28327800/trypanosoma-cruzi-i-genotype-among-isolates-from-patients-with-chronic-chagas-disease-followed-at-the-evandro-chagas-national-institute-of-infectious-diseases-fiocruz-brazil
#6
Tatiana da Silva Fonseca de Oliveira, Barbara Neves Dos Santos, Tainah Silva Galdino, Alejandro Marcel Hasslocher-Moreno, Otilio Machado Pereira Bastos, Maria Auxiliadora de Sousa
INTRODUCTION: Trypanosoma cruzi is the etiologic agent of Chagas disease in humans, mainly in Latin America. Trypanosome stocks were isolated by hemoculture from patients followed at Evandro Chagas National Institute of Infectious Diseases (FIOCRUZ) and studied using different approaches. METHODS: For species and genotype identification, the stocks were analyzed by parasitological techniques, polymerase chain reaction assays targeted to specific DNA sequences, isoenzyme patterns, besides sequencing of a polymorphic locus of TcSC5D gene (one stock)...
January 2017: Revista da Sociedade Brasileira de Medicina Tropical
https://www.readbyqxmd.com/read/28325373/host-parasite-relationships-and-life-histories-of-trypanosomes-in-australia
#7
C Cooper, P L Clode, C Peacock, R C A Thompson
Trypanosomes constitute a group of flagellate protozoan parasites responsible for a number of important, yet neglected, diseases in both humans and livestock. The most significantly studied include the causative agents of African sleeping sickness (Trypanosoma brucei) and Chagas disease (Trypanosoma cruzi) in humans. Much of our knowledge about trypanosome host-parasite relationships and life histories has come from these two human pathogens. Recent investigations into the diversity and life histories of wildlife trypanosomes in Australia highlight that there exists a great degree of biological and behavioural variation within and between trypanosomes...
2017: Advances in Parasitology
https://www.readbyqxmd.com/read/28288771/cattle-breeding-trypanosomosis-prevalence-and-drug-resistance-in-northern-togo
#8
E Tchamdja, A E Kulo, H S Vitouley, K Batawui, A A Bankolé, K Adomefa, G Cecchi, A Hoppenheit, P H Clausen, R De Deken, J Van Den Abbeele, T Marcotty, V Delespaux
African Animal Trypanosomosis (AAT) is a major disease of cattle in Togo and its control is essentially based on chemotherapy. However, because of excessive use of trypanocides during the past decades, chemo-resistance in the parasites has developed. In order to assess the current situation of AAT and resistance to trypanocidal drugs in Northern Togo, a study was conducted on cattle from December 2012 to August 2013 in the regions of Kara and Savanes. An initial cross-sectional survey was carried out in 40 villages using the Haematocrit Centrifugation Technique (HCT)...
March 15, 2017: Veterinary Parasitology
https://www.readbyqxmd.com/read/28263991/selective-inhibition-of-rna-polymerase-i-transcription-as-a-potential-approach-to-treat-african-trypanosomiasis
#9
Louise E Kerry, Elaine E Pegg, Donald P Cameron, James Budzak, Gretchen Poortinga, Katherine M Hannan, Ross D Hannan, Gloria Rudenko
Trypanosoma brucei relies on an essential Variant Surface Glycoprotein (VSG) coat for survival in the mammalian bloodstream. High VSG expression within an expression site body (ESB) is mediated by RNA polymerase I (Pol I), which in other eukaryotes exclusively transcribes ribosomal RNA genes (rDNA). As T. brucei is reliant on Pol I for VSG transcription, we investigated Pol I transcription inhibitors for selective anti-trypanosomal activity. The Pol I inhibitors quarfloxin (CX-3543), CX-5461, and BMH-21 are currently under investigation for treating cancer, as rapidly dividing cancer cells are particularly dependent on high levels of Pol I transcription compared with nontransformed cells...
March 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28257521/exosome-secretion-affects-social-motility-in-trypanosoma-brucei
#10
Dror Eliaz, Sriram Kannan, Hadassa Shaked, Gil Arvatz, Itai Dov Tkacz, Lior Binder, Hiba Waldman Ben-Asher, Uthman Okalang, Vaibhav Chikne, Smadar Cohen-Chalamish, Shulamit Michaeli
Extracellular vesicles (EV) secreted by pathogens function in a variety of biological processes. Here, we demonstrate that in the protozoan parasite Trypanosoma brucei, exosome secretion is induced by stress that affects trans-splicing. Following perturbations in biogenesis of spliced leader RNA, which donates its spliced leader (SL) exon to all mRNAs, or after heat-shock, the SL RNA is exported to the cytoplasm and forms distinct granules, which are then secreted by exosomes. The exosomes are formed in multivesicular bodies (MVB) utilizing the endosomal sorting complexes required for transport (ESCRT), through a mechanism similar to microRNA secretion in mammalian cells...
March 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28249250/stigmasterol-retards-the-proliferation-and-pathological-features-of-trypanosoma-congolense-infection-in-rats-and-inhibits-trypanosomal-sialidase-in-vitro-and-in-silico
#11
Raphael Aminu, Ismaila Alhaji Umar, Md Atiar Rahman, Mohammed Auwal Ibrahim
Stigmasterol has been reported to possess antitrypanosomal activity using in vitro model but information on the in vivo antitrypanosomal effects which is necessary in drug development process has not been evaluated. Hence, the present study investigates the in vivo effects of stigmasterol against T. congolense in addition to its inhibitory effects of trypanosomal sialidase. Stigmasterol, at 100mg/kg BW, did not significantly (p>0.05) reduce the progression of T. congolense infection in animals but a 200mg/kg BW stigmasterol treatment significantly (p<0...
February 26, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28246189/aee788-inhibits-basal-body-assembly-and-blocks-dna-replication-in-the-african-trypanosome
#12
Catherine Sullenberger, Daniel Pique, Yuko Ogata, Kojo Mensa-Wilmot
Trypanosoma brucei causes human African trypanosomiasis (HAT). The pyrrolopyrimidine AEE788 (a hit for anti-HAT drug discovery) associates with three trypanosome protein kinases. Herein we delineate the effects of AEE788 on T. brucei using chemical biology strategies. AEE788 treatment inhibits DNA replication in the kinetoplast (mitochondrial nucleoid) and nucleus. In addition, AEE788 blocks duplication of the basal body and the bilobe without affecting mitosis. Thus, AEE788 prevents entry into S phase of the cell division cycle...
February 28, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28222138/anti-trypanosomal-activity-of-non-peptidic-nitrile-based-cysteine-protease-inhibitors
#13
Antonio C B Burtoloso, Sérgio de Albuquerque, Mark Furber, Juliana C Gomes, Cristiana Gonçalez, Peter W Kenny, Andrei Leitão, Carlos A Montanari, José Carlos Quilles, Jean F R Ribeiro, Josmar R Rocha
The cysteine protease cruzipain is considered to be a validated target for therapeutic intervention in the treatment of Chagas disease. Anti-trypanosomal activity against the CL Brener strain of T. cruzi was observed in the 0.1 μM to 1 μM range for three nitrile-based cysteine protease inhibitors based on two scaffolds known to be associated with cathepsin K inhibition. The two compounds showing the greatest potency against the trypanosome were characterized by EC50 values (0.12 μM and 0.25 μM) that were an order of magnitude lower than the corresponding Ki values measured against cruzain, a recombinant form of cruzipain, in an enzyme inhibition assay...
February 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28212935/dissecting-biochemical-peculiarities-of-the-atpase-activity-of-tcsub2-a-component-of-the-mrna-export-pathway-in-trypanosoma-cruzi
#14
Ize de Aguiar Bittencourt, Mariana Serpeloni, Priscila Mazzochi Hiraiwa, Tatiana de Arruda Campos Brasil de Souza, Andréa Rodrigues Ávila
The RNA helicase DEAD-box protein Sub2 (yeast)/UAP56 (mammals) is conserved across eukaryotes and is essential for mRNA export in trypanosomes. Despite the high conservation of Sub2 in lower eukaryotes such as Trypanosoma cruzi, the low conservation of other mRNA export factors raises questions regarding whether the mode of action of TcSub2 is similar to that of orthologs from other eukaryotes. Mutation of the conserved K87 residue of TcSub2 abolishes ATPase activity, showing that its ATPase domain is functional...
May 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28194625/trypanosomiasis-challenge-estimation-using-the-diminazene-aceturate-berenil-index-in-zebu-in-gabon
#15
Brieuc G A Cossic, Brice Adjahoutonon, Pierre Gloaguen, Gui Lov Dibanganga, Gael Maganga, Pascal Leroy, Ewan T MacLeod, Kim Picozzi
A longitudinal study was conducted within a cattle ranch in Gabon to determine the diminazene aceturate (Berenil) index (DAI) in a group of Zebu, raised under low tsetse density; this measure providing an assessment of trypanosomiasis risk. The objective was to evaluate the trypanosomiasis pressure thus informing trypanosomiasis control methods and cattle management. Twenty female adult Zebu were monitored for 24 weeks during the dry season. Blood samples were collected on a weekly basis and subjected to parasitological and haematological analysis (n = 480), using the buffy-coat method and the packed cell volume value (PCV), respectively, infected animals were treated with a single intramuscular injection of diminazene aceturate (8 mg/kg)...
March 2017: Tropical Animal Health and Production
https://www.readbyqxmd.com/read/28177042/microbial-control-of-arthropod-borne-disease
#16
Miguel A Saldaña, Shivanand Hegde, Grant L Hughes
Arthropods harbor a diverse array of microbes that profoundly influence many aspects of host biology, including vector competence. Additionally, symbionts can be engineered to produce molecules that inhibit pathogens. Due to their intimate association with the host, microbes have developed strategies that facilitate their transmission, either horizontally or vertically, to conspecifics. These attributes make microbes attractive agents for applied strategies to control arthropod-borne disease. Here we discuss the recent advances in microbial control approaches to reduce the burden of pathogens such as Zika, Dengue and Chikungunya viruses, and Trypanosome and Plasmodium parasites...
February 2017: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/28167559/anti-trypanosomal-activity-of-sterol-14%C3%AE-demethylase-cyp51-inhibitors-vni-and-vfv-in-the-swiss-mouse-models-of-chagas-disease-induced-by-the-y-strain-trypanosoma-cruzi
#17
F H Guedes-da-Silva, D G J Batista, C F Da Silva, J S De Araújo, B P Pavão, M R Simões-Silva, M B Meuser, K C Demarque, O C Moreira, C Britto, G I Lepesheva, M N C Soeiro
Chagas disease is a life-threatening infection caused by a variety of genetically diverse strains of the protozoan parasite Trypanosoma cruzi The current treatment (benznidazole and nifurtimox) is unsatisfactory, and potential alternatives include inhibitors of sterol 14α-demethylase (CYP51), the cytochrome P450 enzyme essential for biosynthesis of sterols in eukaryotes and the major target for clinical and agricultural antifungals. Here we performed a comparative investigation of two protozoa-specific CYP51 inhibitors, VNI and its CYP51 structure-based derivative VFV, in the murine models of infection caused by the Y strain T...
February 6, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28166845/let-s-get-fissical-fast-in-silico-synchronization-as-a-new-tool-for-cell-division-cycle-analysis
#18
Brooke Morriswood, Markus Engstler
Cell cycle progression is a question of fundamental biological interest. The coordinated duplication and segregation of all cellular structures and organelles is however an extremely complex process, and one which remains only partially understood even in the most intensively researched model organisms. Trypanosomes are in an unusual position in this respect - they are both outstanding model systems for fundamental questions in eukaryotic cell biology, and pathogens that are the causative agents of three of the neglected tropical diseases...
February 7, 2017: Parasitology
https://www.readbyqxmd.com/read/28162093/evaluating-the-impact-of-targeting-livestock-for-the-prevention-of-human-and-animal-trypanosomiasis-at-village-level-in-districts-newly-affected-with-t-b-rhodesiense-in-uganda
#19
Louise Hamill, Kim Picozzi, Jenna Fyfe, Beatrix von Wissmann, Sally Wastling, Nicola Wardrop, Richard Selby, Christine Amongi Acup, Kevin L Bardosh, Dennis Muhanguzi, John D Kabasa, Charles Waiswa, Susan C Welburn
BACKGROUND: Uganda has suffered from a series of epidemics of Human African Trypanosomiasis (HAT), a tsetse transmitted disease, also known as sleeping sickness. The area affected by acute Trypanosoma brucei rhodesiense HAT (rHAT) has been expanding, driven by importation of infected cattle into regions previously free of the disease. These regions are also affected by African Animal Trypanosomiasis (AAT) demanding a strategy for integrated disease control. METHODS: In 2008, the Public Private Partnership, Stamp Out Sleeping Sickness (SOS) administered a single dose of trypanocide to 31 486 head of cattle in 29 parishes in Dokolo and Kaberamaido districts...
February 6, 2017: Infectious Diseases of Poverty
https://www.readbyqxmd.com/read/28145221/molecular-identification-of-trypanosome-species-in-trypanotolerant-cattle-from-the-south-of-gabon
#20
Gaël Darren Maganga, Jacques-François Mavoungou, Nadine N'dilimabaka, Ivan Cyr Moussadji Kinga, Bertrand Mvé-Ondo, Illich Manfred Mombo, Barthélémy Ngoubangoye, Brieuc Cossic, Clency Sylde Mikala Okouyi, Alain Souza, Eric Maurice Leroy, Brice Kumulungui, Benjamin Ollomo
The aim of this study was to provide information on trypanosome species infecting trypanotolerant cattle from southern Gabon. The study was conducted on 224 trypanotolerant cattle from three regions located in southern Gabon, using ITS1 primer-based PCR. Seventy-two (32%) N'dama cattle were found polymerase chain reaction (PCR) positive with trypanosomes. The overall prevalence of trypanosomosis was 57% (63/110), 4% (4/100), and 36% (5/14) in the Gala section of the Nyanga ranch, the Miyama ranch, and Ossiele, respectively...
2017: Parasite: Journal de la Société Française de Parasitologie
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