Suchergebnisse

This work was financially supported by the Ministry of Economy and Competitiveness of Spain co-financed with European Regional Development Funds (References: CGL2015-71709-R and SAF2015-71714-R) and the fellowship PEJ2018-004702-A. The European Union also collaborated in the funding of this study (Euronanomed programme, Reference: TARBRAINFECT, and Innovative Medicines Initiative IMI2, Reference: 3TR-831434), as well as the Health Institute Carlos III as the local management institution (Reference: AC18/00008). A.S.L. and V.S.M. were supported by a fellowship from the Ministry of Education, Culture and Sport (FPU 17/05413 and FPU 16/05822), and the results presented in this article are part of A.S.L's doctoral thesis. M.O.G acknowledges for the funds received by the F.P.U. fellowship provided by University of Almeria. ; Next generation sequencing methods are widely used in evaluating the structure and functioning of microbial communities, especially those centered on 16S rRNA subunit. Since Illumina Miseq, the most used sequencing platform, does not allow the full sequencing of 16S rRNA gene, this study aims to evaluate whether the choice of different target regions might affect the outcome of microbiome studies regarding soil and saliva samples. V1V3, V3V4, V4V5 and V6V8 domains were studied, finding that while some regions showed differences in the detection of certain bacterial taxa and in the calculation of alpha diversity, especially in soil samples, the overall effect did not compromise the differentiation of any sample type in terms of taxonomic analysis at the genus level. 16S rRNA target regions did affect the detection of specific bacteria related to soil quality and development, and microbial genera used as health biomarkers in saliva. V1V3 region showed the closest similarity to internal sequencing control mock community B, suggesting it might be the most preferable choice regarding data reliability. ; European Union (EU) 3TR-831434 ; Instituto de Salud Carlos III AC18/00008 ; Ministry of Education, Culture and Sport FPU 17/05413 FPU 16/05822 ; University of Almeria ; Ministry of Economy and Competitiveness of Spain ; European Union (EU) CGL2015-71709-R SAF2015-71714-R PEJ2018-004702-A

Sleeping sickness or African trypanosomiasis is a serious health concern with an added socio-economic impact in sub-Saharan Africa due to direct infection in both humans and their domestic livestock. There is no vaccine available against African trypanosomes and its treatment relies only on chemotherapy. Although the current drugs are effective, most of them are far from the modern concept of a drug in terms of toxicity, specificity and therapeutic regime. In a search for new molecules with trypanocidal activity, a high throughput screening of 2000 microbial extracts was performed. Fractionation of one of these extracts, belonging to a culture of the fungus Amesia sp., yielded a new member of the curvicollide family that has been designated as curvicollide D. The new compound showed an inhibitory concentration 50 (IC50) 16-fold lower in Trypanosoma brucei than in human cells. Moreover, it induced cell cycle arrest and disruption of the nucleolar structure. Finally, we showed that curvicollide D binds to DNA and inhibits transcription in African trypanosomes, resulting in cell death. These results constitute the first report on the activity and mode of action of a member of the curvicollide family in T. brucei. ; European Union (Euronanomed programme, Reference: TARBRAINFECT) ; Health Carlos III as the local management institution AC18/00008 ; Ministry of Science, Innovation and Universities from Spain PID2020-120481RB-I00 ; Ministry of Education, Culture and Sport FPU 17/05413 FPU 16/05822 FPU 20/03952 ; University of Almeria FPI-201102 PPUENTE2021-006