Recombinant production, crystallization and crystal structure determination of dihydroorotate dehydrogenase from Leishmania (Viannia) braziliensis

In this study, a reproducible protocol for the heterologous expression of active dihydroorotate dehydrogenase from Leishmania (Viannia) braziliensis (LbDHODH) was developed and its crystal structure was determined at 2.12 Å resolution. L. (V.) braziliensis is the species responsible for the mucosal form of leishmaniasis, a neglected disease for which no cure or effective therapy is available. Analyses of sequence, structural and kinetic features classify LbDHODH as a member of the class 1A DHODHs and reveal a very high degree of structural conservation with the previously reported structures of orthologous trypanosomatid enzymes. The relevance of nucleotide-biosynthetic pathways for cell metabolism together with structural and functional differences from the respective host enzyme suggests that inhibition of LbDHODH could be exploited for antileishmanicidal drug development. The present work provides the framework for further integrated in vitro, in silico and in vivo studies as a new tool to evaluate DHODH as a drug target against trypanosomatid-related diseases.
Source: Acta Crystallographica Section F - Category: Biochemistry Authors: Tags: dihydroorotate dehydrogenase Leishmania (Viannia) braziliensis leishmaniasis research communications Source Type: research

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J, Gomez MA Abstract Multiple PCR-based approaches have been developed for Leishmania detection in clinical and laboratory samples, and this diversity limits inter-study comparisons, meta-analyses, and generalization of findings. Toward the harmonization of a molecular tool for detection of Leishmania (Viannia) for research purposes, we evaluated the concordance of 18SrDNA qPCR and minicircle kinetoplastid DNA (mkDNA) PCR followed by Southern blot (PCR-SB) in in vitro infection systems and in lesion and mucosal swab samples from Colombian patients with cutaneous leishmaniasis caused by L. (Viannia). The lower limi...
Source: The American Journal of Tropical Medicine and Hygiene - Category: Tropical Medicine Authors: Tags: Am J Trop Med Hyg Source Type: research
We describe two new patients with ML diagnosed in New York City-a Syrian immigrant with a nasal mass (Leishmania tropica), the first report of Old World ML in the United States, and an American ecologist who worked in Bolivia and had been treated for cutaneous infection 23 years before developing lesions (L. (Viannia) braziliensis) initially of the uvula, soft palate, and posterior pharynx and subsequently the larynx. PMID: 32228792 [PubMed - as supplied by publisher]
Source: The American Journal of Tropical Medicine and Hygiene - Category: Tropical Medicine Authors: Tags: Am J Trop Med Hyg Source Type: research
We examined the pattern of toll-like receptor 2 (TLR2), TLR4, TLR7, interleukin- (IL-) 10, interferon gamma (IFN-γ), and (program death ligand) PD-L1 gene expression in LST-positive reactions and paired normal-looking skin of nine infected Ibizan hound dogs. Healthy skin from ten seronegative dogs from a nonendemic area was analysed as a negative control. Immune gene expressions were examined by quantitative PCR (qPCR) analysis. LST-positive reactions presented significant upregulation of TLR2, TLR4, IL-10, IFN-γ, and PD-L1 and downregulation of TLR7 when compared with healthy skin of seronegative control dogs ...
Source: Journal of Immunology Research - Category: Allergy & Immunology Tags: J Immunol Res Source Type: research
Publication date: Available online 25 March 2020Source: Biochimica et Biophysica Acta (BBA) - General SubjectsAuthor(s): Carlos A.H. Fernandes, Edna Gicela O. Morea, Gabriel A. dos Santos, Vitor L. da Silva, Marina Roveri Vieira, Maria Alejandra Viviescas, Jean Chatain, Aurélie Vadel, Carole Saintomé, Marcos Roberto M. Fontes, Maria Isabel Nogueira Cano
Source: Biochimica et Biophysica Acta (BBA) General Subjects - Category: Biochemistry Source Type: research
Publication date: 24 March 2020Source: Cell Reports, Volume 30, Issue 12Author(s): Inês Mesquita, Carolina Ferreira, Diana Moreira, George Eduardo Gabriel Kluck, Ana Margarida Barbosa, Egídio Torrado, Ricardo Jorge Dinis-Oliveira, Luís Gafeira Gonçalves, Charles-Joly Beauparlant, Arnaud Droit, Luciana Berod, Tim Sparwasser, Neelam Bodhale, Bhaskar Saha, Fernando Rodrigues, Cristina Cunha, Agostinho Carvalho, António Gil Castro, Jérôme Estaquier, Ricardo Silvestre
Source: Cell Reports - Category: Cytology Source Type: research
Publication date: Available online 24 March 2020Source: Biological ControlAuthor(s): Tharaka Wijerathna, Samadhi Gunathunga, Nayana Gunathilaka
Source: Biological Control - Category: Biology Source Type: research
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Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research
ConclusionOur results support the role ofPh.longicuspis,Ph.perfiliewi, andPh.perniciosus inL.infantum transmission. Furthermore, these species could be involved inL.major andL.killicki life cycles. The combination of the parasite detection and the blood meal analysis in this study highlights the incrimination of the identified vertebrate inLeishmania transmission. In addition, we quantify for the first time the parasite load in naturally infected sand flies caught in Tunisia. These findings are relevant for a better understanding ofL.infantum transmission cycle in the country. Further investigations and control measures ar...
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research
ConclusionsThese results demonstrate that the thymus of dogs can be parasitized byL. infantum, which may generate inflammatory reactions leading to alterations in thymic microarchitecture.
Source: Immunity, Inflammation and Disease - Category: Allergy & Immunology Authors: Tags: ORIGINAL RESEARCH Source Type: research
This study reveals greater genetic diversity than suggested by geographically-focused studies, provides a resource of genomic variation for future work and sets the scene for a new understanding of the evolution and genetics of theLeishmania donovani complex.
Source: eLife - Category: Biomedical Science Tags: Genetics and Genomics Microbiology and Infectious Disease Source Type: research
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