Phosphoproteomic analysis of mammalian infective Trypanosoma brucei subjected to heat shock suggests atypical mechanisms for thermotolerance.

We report the first quantitative study of changes in protein and phosphorylation site abundance in response to heat shock in the clinically relevant form of the human parasite Trypanosoma brucei. The identification of heat shock responsive phosphorylation sites on proteins with putative roles in thermotolerance including the ZC3H11-MKT1 complex provides evidence of the role dynamic phosphorylation of RNA binding proteins in co-ordinating heat shock. Temperature changes in the host are a major physiological challenge to parasites and factors conferring tolerance to heat shock constitute overlooked virulence factors. A better understanding of these virulence factors will pave the way for the development of novel drug therapies which selectively target T. brucei. PMID: 32198071 [PubMed - as supplied by publisher]
Source: Journal of Proteomics - Category: Biochemistry Authors: Tags: J Proteomics Source Type: research

Related Links:

We report here the identification spiro-containing derivatives as inhibitors of TR fromTrypanosoma brucei (TbTR), the parasite responsible for Human African Trypanosomiasis. The hit series, identified by high throughput screening, was shown to bindTbTR reversibly and to compete with the trypanothione (TS2) substrate. The prototype compound 1 from this series was also found to impede the growth ofTrypanosoma brucei parasitesin vitro. The X-ray crystal structure ofTbTR in complex with compound 1 solved at 1.98 Å allowed the identification of the hydrophobic pocket where the inhibitor binds, placed close to the catalyti...
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research
Abstract Pactamycin and jogyamycin are aminocyclopentitol natural products, where each core carbon bears a stereodefined alcohol or amine moiety. Their structural complexity, coupled with the diversity of functional groups co-existing in a condensed space, make them fascinating synthetic targets in their own right. Pactamycin and its derivatives bind to the 30S ribosomal subunit and display activity against parasites responsible for drug-resistant malaria and African sleeping sickness; however, efforts to develop their therapeutic potential have been hampered by their cellular toxicity. Interestingly, bioengineere...
Source: Angewandte Chemie - Category: Chemistry Authors: Tags: Angew Chem Int Ed Engl Source Type: research
Animal African trypanosomiasis (AAT) is a life-threatening vector-borne disease, caused by trypanosome parasites, which are principally transmitted by tsetse flies. In Kenya, the prevalence of drug-resistant t...
Source: BMC Research Notes - Category: Research Authors: Tags: Research note Source Type: research
ari R Abstract In this paper, starting from the reversible rhodesain inhibitors 1a-c endowed with K i values in the low micromolar range towards the target protease, we now designed a new series of peptidomimetics 2a-g containing the benzodiazepine scaffold as a β -turn mimetic, and characterized by a specific peptide sequence for the inhibition of rhodesain. Considering that an irreversible inhibition is strongly desirable in the case of a parasitic target, a vinyl ester moiety acting as Michael-acceptor has been introduced as the warhead; finally, this portion has been functionalized in order to evaluate th...
Source: ChemMedChem - Category: Chemistry Authors: Tags: ChemMedChem Source Type: research
Abstract Trypanosomatids are unicellular parasitic protozoa. Many of the species of this genera cause severe diseases in human, such as Leishmaniasis, African trypanosomiasis and Chagas disease. These parasites possess a single reticular mitochondrion with a concatenated structure of mitochondrial DNA known as kinetoplast or kDNA. kDNA encodes few essential mitochondrial proteins but no tRNAs. Therefore, trypanosomatid mitochondrion import a full set of nucleus-encoded tRNAs for mitochondrial translation. Recent advances indicated that mitochondrial protein translocases, particularly the subunits of the ATOM compl...
Source: Gene - Category: Genetics & Stem Cells Authors: Tags: Gene Source Type: research
Abstract The Trypanosomatid family are a diverse and widespread group of protozoan parasites that belong to the higher order class Kinetoplastida. Containing predominantly monoxenous species (i.e. those having only a single host) that are confined to invertebrate hosts, this class is primarily known for its pathogenic dixenous species (i.e. those that have two hosts), serving as the aetiological agents of the important neglected tropical diseases (NTDs) including leishmaniasis, American trypanosomiasis (Chagas disease) and human African trypanosomiasis. Over the past few decades, a multitude of studies have invest...
Source: International Journal for Parasitology - Category: Parasitology Authors: Tags: Int J Parasitol Source Type: research
Abstract Human African trypanosomiasis (HAT) is a deadly neglected tropical disease caused by the protozoan parasite Trypanosoma brucei. During the course of screening a collection of diverse nitrogenous heterocycles, we discovered two novel compounds that contain the tetracyclic core of the Yohimbine and Corynanthe alkaloids, were potent inhibitors of T. brucei proliferation and T. brucei methionyl-tRNA synthetase (TbMetRS) activity. Inspired by these key findings, we prepared several novel series of hydroxyalkyl δ-lactam, δ-lactam, and piperidine analogs and tested their anti-trypanosomal activity. A...
Source: Tetrahedron - Category: Chemistry Authors: Tags: Tetrahedron Source Type: research
Abstract Elimination programs targeting TriTryp diseases (Leishmaniasis, Chagas' disease, human African trypanosomiasis) significantly reduced the number of cases. Continued surveillance is crucial to sustain this progress, but parasite molecular surveillance by genotyping is currently lacking. We explain here which epidemiological questions of public health and clinical relevance could be answered by means of molecular surveillance. Whole-genome sequencing (WGS) for molecular surveillance will be an important added value, where we advocate that preference should be given to direct sequencing of the parasite's gen...
Source: Trends in Parasitology - Category: Parasitology Authors: Tags: Trends Parasitol Source Type: research
Conclusion: This study is one of the first studies related to the production of Trypanosoma species in Turkey and planned to provide a basis for the studies of African sleeping disease, Chagas disease and their agents. PMID: 32212582 [PubMed - as supplied by publisher]
Source: Turkish Society for Parasitology - Category: Parasitology Authors: Tags: Turkiye Parazitol Derg Source Type: research
by Madison Elle Walsh, Eleanor Mary Naudzius, Savanah Jessica Diaz, Theodore William Wismar, Mikhail Martchenko Shilman, Danae SchulzTrypanosoma brucei are unicellular parasites endemic to Sub-Saharan Africa that cause fatal disease in humans and animals. Infection with these parasites is caused by the bite of the tsetse fly vector, and parasites living extracellularly in the blood of infected animals evade the host immune system through antigenic variation. Existing drugs for Human and Animal African Trypanosomiasis are difficult to administer and can have serious side effects. Resistance to some drugs is also increasing,...
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research
More News: African Health | African Sleeping Sickness | Biochemistry | Parasitic Diseases | Parasitology | Science | Sleeping Sickness | Study