Researchers engineer a cost-effective treatment for neglected tropical disease


(University of Tokyo) Researchers have turned a fungus into a disease-curing factory through modern genetic engineering and patience. The natural antibiotic is a promising cure for a neglected tropical disease called human African trypanosomiasis, or African sleeping sickness, that infects thousands of people in remote, rural areas of sub-Saharan Africa each year.

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by Kelita Kamoto, Harry Noyes, Peter Nambala, Edward Senga, Janelisa Musaya-Mwalija, Benjamin Kumwenda, Bruno Bucheton, Annette Macleod, Christiane Herz-Fowler, Enock Matovu, Arthur M. Chiwaya, John E. Chisi, for the TrypanoGEN Research Group as members of The H3Africa ConsortiumTrypanosoma brucei (T.b.) rhodesiense is the cause of the acute form of human African trypanosomiasis (HAT) in eastern and southern African countries. There is some evidence that there is diversity in the disease progression ofT.b.rhodesiense in different countries. HAT in Malawi is associated with a chronic haemo-lymphatic stage infection compared…

by Richard Selby, Charles Wamboga, Olema Erphas, Albert Mugenyi, Vincent Jamonneau, Charles Waiswa, Steve J. Torr, Michael Lehane

In 1994, combined active and passive screening reported 1469 cases from the historic Gambian Human African Trypanosomiasis (gHAT) foci of West Nile, Uganda. Since 2011 systematic active screening has stopped and there has been reliance on passive screening. During 2014, passive screening alone det ected just nine cases. In the same year a tsetse control intervention was expanded to cover the main gHAT foci in West Nile to curtail transmission of gHAT contributing to the elimination of gHAT as a…

Abstract
Trypanothione reductase (TR) plays a key role in the unique redox metabolism of trypanosomatids, the causative agents of human African trypanosomiasis (HAT), Chagas’ disease, and leishmaniases. Introduction of a new, lean propargylic vector to a known class of TR inhibitors resulted in the strongest reported competitive inhibitor of Trypanosoma (T.) brucei TR, with an inhibition constant Ki of 73 nm, which is fully selective against human glutathione reductase (hGR). The best ligands exhibited in vitro IC50 values (half-maximal inhibitory concentration) against the HAT pathogen, T. brucei rhodesiense, i…

Source: ChemistryCategory: Chemistry Authors: Tags: Chemistry Source Type: research

Publication date: Available online 1 August 2019Source: Protein Expression and PurificationAuthor(s): Lauren E-A. Eyssen, Theresa H.T. CoetzerAbstractThe metacaspases (MCAs) are attractive drug targets for the treatment of African trypanosomiasis as they are not found in the metazoan kingdom and their action has been implicated in cell cycle and cell death pathways in kinetoplastid parasites. Here we report the biochemical characterisation of MCA5 from T. congolense. Upon recombinant expression in E. coli, autoprocessing is evident, and MCA5 further autoprocesses when purified using nickel affinity chromatography, which we…

Wow – we received so many excellent comments on how parasites and the number 5 go together! Here are many of them – in no particular order – for your viewing pleasure:Pentatrichomonas hominis is a nonpathogenic intestinal flagellate named for its 5 flagella (penta from the Greek pente, meaning five + trich, pertaining to hair [flagella]). By Neil Anderson and Bernardino Rocha.There are 5 lobes of the lung, and all can be infected by Paragonimusspecies. By Brian Duresko.The are 5Plasmodiumspecies that are responsible for the bulk of malaria in humans:P. falciparum, P. vivax, P. ovale, P. malariae, andP. knowlesi(t…

a Silva

Dithiocarbamates represent a class of compounds that were evaluated in different biomedical applications because of their chemical versatility. For this reason, several pharmacological activities have already been attributed to these compounds, such as antiparasitic, antiviral, antifungal activities, among others. Therefore, compounds that are based on dithiocarbamates have been evaluated in different in vivo and in vitro models as potential new antimicrobials. Thus, the purpose of this review is to present the possibilities of using dithiocarbamate compounds as potential new antitrypanosomatids-drugs, which co…

Source: MoleculesCategory: Chemistry Authors: Tags: Review Source Type: research

by Daniela I. Schneider, Norah Saarman, Maria G. Onyango, Chaz Hyseni, Robert Opiro, Richard Echodu, Michelle O ’Neill, Danielle Bloch, Aurélien Vigneron, T. J. Johnson, Kirstin Dion, Brian L. Weiss, Elizabeth Opiyo, Adalgisa Caccone, Serap Aksoy

Tsetse flies (Glossina spp.) are vectors of parasitic trypanosomes, which cause human (HAT) and animal African trypanosomiasis (AAT) in sub-Saharan Africa. In Uganda,Glossina fuscipes fuscipes (Gff) is the main vector of HAT, where it transmits Gambiense disease in the northwest and Rhodesiense disease in central, southeast and western regions. Endosymbionts can infl…

Publication date: Available online 29 July 2019Source: Biochimica et Biophysica Acta (BBA) – Molecular Cell ResearchAuthor(s): Vishal C. Kalel, Mengqiao Li, Stefan Gaussmann, Florent Delhommel, Ann-Britt Schäfer, Bettina Tippler, Martin Jung, Renate Maier, Silke Oeljeklaus, Wolfgang Schliebs, Bettina Warscheid, Michael Sattler, Ralf ErdmannAbstractTrypanosomatid parasites cause devastating African sleeping sickness, Chagas disease, and Leishmaniasis that affect about 18 million people worldwide. Recently, we showed that the biogenesis of glycosomes could be the “Achilles’ heel” of trypanosomatids suitable …

Antitrypanosomal Effects of Zanthoxylum zanthoxyloides (Lam.) Zepern. &Timler Extracts on African Trypanosomes.
Evid Based Complement Alternat Med. 2019;2019:1730452
Authors: Dofuor AK, Djameh GI, Ayertey F, Bolah P, Amoa-Bosompem M, Kyeremeh K, Okine LK, Gwira TM, Ohashi M
Abstract
African trypanosomiasis is a disease caused by the parasitic protozoa of the Trypanosoma genus. Despite several efforts at chemotherapeutic interventions, the disease poses serious health and economic concerns to humans and livestock of many sub-Saharan African countries. Zanthoxylum zanthoxyloides (Lam.) Zepern. &T…

This study conducted a population genetic study using partial mitochondrial cytochrome oxidase gene 1 (CO1) and 10 microsatellite loci to investigate the genetic diversity and population structure ofG.m.morsitans captured in the major HAT foci in Zambia and Malawi. We have included 108 and 99G.m.morsitans samples for CO1 and microsatellite analyses respectively. Our results suggest the presence of two different genetic clusters ofG.m.morsitans, existing East and West of the escarpment of the Great Rift Valley. We have also revealed genetic similarity between theG.m.morsitans in Kasungu National Park and those in the Luangw…



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