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1.
J Biol Chem ; 299(6): 104715, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37061002

RESUMEN

Trypanosomatids are a diverse group of uniflagellate protozoan parasites that include globally relevant pathogens such as Trypanosoma cruzi, the causative agent of Chagas disease. Trypanosomes lack the fatty acid synthase system typically used for de novo fatty acid (FA) synthesis in other eukaryotes. Instead, these microbes have evolved a modular FA elongase (ELO) system comprised of individual ELO enzymes (ELO1-4) that can operate processively to generate long chain- and very long chain-FAs. The importance of ELO's for maintaining lipid homeostasis in trypanosomatids is currently unclear, given their ability to take up and utilize exogenous FAs for lipid synthesis. To assess ELO function in T. cruzi, we generated individual KO lines, Δelo1, Δelo2, and Δelo3, in which the genes encoding ELO1-3 were functionally disrupted in the parasite insect stage (epimastigote). Using unbiased lipidomic and metabolomic analyses, in combination with metabolic tracing and biochemical approaches, we demonstrate that ELO2 and ELO3 are required for global lipid homeostasis, whereas ELO1 is dispensable for this function. Instead, ELO1 activity is needed to sustain mitochondrial activity and normal growth in T. cruzi epimastigotes. The cross-talk between microsomal ELO1 and the mitochondrion is a novel finding that, we propose, merits further examination of the trypanosomatid ELO pathway as critical for central metabolism.


Asunto(s)
Enfermedad de Chagas , Trypanosoma cruzi , Humanos , Trypanosoma cruzi/genética , Trypanosoma cruzi/metabolismo , Elongasas de Ácidos Grasos/metabolismo , Enfermedad de Chagas/genética , Enfermedad de Chagas/metabolismo , Homeostasis , Mitocondrias/genética , Mitocondrias/metabolismo , Lípidos
2.
PLoS Negl Trop Dis ; 12(2): e0006243, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29462134

RESUMEN

Triatomines are hematophagous arthropod vectors of Trypanosoma cruzi, the causative agent of Chagas Disease. Panstrongylus lignarius, also known as Panstrongylus herreri, is considered one of the most versatile triatomines because it can parasitize different hosts, it is found in different habitats and countries, it has sylvatic, peridomestic and domestic behavior and it is a very important vector of Chagas disease, especially in Peru. Molecules produced and secreted by salivary glands and fat body are considered of important adaptational value for triatomines because, among other functions, they subvert the host haemostatic, inflammatory and immune systems and detoxify or protect them against environmental aggressors. In this context, the elucidation of the molecules produced by these tissues is highly valuable to understanding the ability of this species to adapt and transmit pathogens. Here, we use high-throughput sequencing techniques to assemble and describe the coding sequences resulting from the transcriptome of the fat body and salivary glands of P. lignarius. The final assembly of both transcriptomes together resulted in a total of 11,507 coding sequences (CDS), which were mapped from a total of 164,676,091 reads. The CDS were subdivided according to their 10 folds overexpression on salivary glands (513 CDS) or fat body (2073 CDS). Among the families of proteins found in the salivary glands, lipocalins were the most abundant. Other ubiquitous families of proteins present in other sialomes were also present in P. lignarius, including serine protease inhibitors, apyrase and antigen-5. The unique transcriptome of fat body showed proteins related to the metabolic function of this organ. Remarkably, nearly 20% of all reads mapped to transcripts coded by Triatoma virus. The data presented in this study improve the understanding on triatomines' salivary glands and fat body function and reveal important molecules used in the interplay between vectors and vertebrate hosts.


Asunto(s)
Cuerpo Adiposo/metabolismo , Panstrongylus/genética , Glándulas Salivales/metabolismo , Transcriptoma , Animales , Enfermedad de Chagas/transmisión , Perfilación de la Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento , Proteínas de Insectos/genética , Insectos Vectores/genética , Insectos Vectores/metabolismo , Lipocalinas/genética , Panstrongylus/anatomía & histología , Panstrongylus/metabolismo , Perú , Proteómica , Proteínas y Péptidos Salivales/genética , Proteínas y Péptidos Salivales/metabolismo , Inhibidores de Serina Proteinasa/genética , Inhibidores de Serina Proteinasa/metabolismo
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