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Metadados | Descrição | Idioma |
---|---|---|
Autor(es): dc.contributor | Robert Koch Inst | - |
Autor(es): dc.contributor | Univ Edinburgh | - |
Autor(es): dc.contributor | Univ Glasgow | - |
Autor(es): dc.contributor | Univ Melbourne | - |
Autor(es): dc.contributor | Universidade Estadual Paulista (Unesp) | - |
Autor(es): dc.contributor | Leibniz Inst Mol Pharmacol | - |
Autor(es): dc.creator | Semini, Geo | - |
Autor(es): dc.creator | Paape, Daniel | - |
Autor(es): dc.creator | Blume, Martin | - |
Autor(es): dc.creator | Sernee, M. Fleur | - |
Autor(es): dc.creator | Peres-Alonso, Diego [UNESP] | - |
Autor(es): dc.creator | Calvignac-Spencer, Sebastien | - |
Autor(es): dc.creator | Doellinger, Joerg | - |
Autor(es): dc.creator | Jehle, Stefan | - |
Autor(es): dc.creator | Saunders, Eleanor | - |
Autor(es): dc.creator | McConville, Malcolm J. | - |
Autor(es): dc.creator | Aebischer, Toni | - |
Data de aceite: dc.date.accessioned | 2022-02-22T00:56:42Z | - |
Data de disponibilização: dc.date.available | 2022-02-22T00:56:42Z | - |
Data de envio: dc.date.issued | 2021-06-25 | - |
Data de envio: dc.date.issued | 2021-06-25 | - |
Data de envio: dc.date.issued | 2020-05-01 | - |
Fonte completa do material: dc.identifier | http://dx.doi.org/10.1128/mBio.01057-20 | - |
Fonte completa do material: dc.identifier | http://hdl.handle.net/11449/209482 | - |
Fonte: dc.identifier.uri | http://educapes.capes.gov.br/handle/11449/209482 | - |
Descrição: dc.description | Leishmania spp. are protozoan parasites that cause a spectrum of important diseases in humans. These parasites develop as extracellular promastigotes in the digestive tract of their insect vectors and as obligate intracellular amastigotes that infect macrophages and other phagocytic cells in their vertebrate hosts. Promastigote-to-amastigote differentiation is associated with marked changes in metabolism, including the upregulation of enzymes involved in fatty acid beta-oxidation, which may reflect adaptation to the intracellular niche. Here, we have investigated the function of one of these enzymes, a putative 2,4-dienoyl-coenzyme A (CoA) reductase (DECR), which is specifically required for the beta-oxidation of polyunsaturated fatty acids. The Leishmania DECR shows close homology to bacterial DECR proteins, suggesting that it was acquired by lateral gene transfer. It is present in other trypanosomatids that have obligate intracellular stages (i.e., Trypanosoma cruzi and Angomonas) but is absent from dixenous parasites with an exclusively extracellular lifestyle (i.e., Trypanosoma brucer). A DECR-green fluorescent protein (GFP) fusion protein was localized to the mitochondrion in both promastigote and amastigote stages, and the levels of expression increased in the latter stages. A Leishmania major Delta decr null mutant was unable to catabolize unsaturated fatty acids and accumulated the intermediate 2,4-decadienoyl-CoA, confirming DECR's role in beta-oxidation. Strikingly, the L. major Delta decr mutant was unable to survive in macrophages and was avirulent in BALB/c mice. These findings suggest that beta-oxidation of polyunsaturated fatty acids is essential for intracellular parasite survival and that the bacterial origin of key enzymes in this pathway could be exploited in developing new therapies. IMPORTANCE The Trypanosomatidae are protozoan parasites that infect insects, plants, and animals and have evolved complex monoxenous (single host) and dixenous (two hosts) lifestyles. A number of species of Trypanosomatidae, including Leishmania spp., have evolved the capacity to survive within intracellular niches in vertebrate hosts. The adaptations, metabolic and other, that are associated with development of intracellular lifestyles remain poorly defined. We show that genomes of Leishmania and Trypanosomatidae that can survive intracellularly encode a 2,4-dienoyl-CoA reductase that is involved in catabolism of a subclass of fatty acids. The trypanosomatid enzyme shows closest similarity to the corresponding bacterial enzymes and is located in the mitochondrion and essential for intracellular growth of Leishmania. The findings suggest that acquisition of this gene by lateral gene transfer from bacteria by ancestral monoxenous Trypanosomatidae likely contributed to the development of a dixenous lifestyle of these parasites. | - |
Descrição: dc.description | Federal Ministry of Education and Research (BMBF) | - |
Descrição: dc.description | DFG research fellowship | - |
Descrição: dc.description | European Commission Marie Curie Excellence grant | - |
Descrição: dc.description | Deutsche Forschungsgemeinschaft | - |
Descrição: dc.description | Robert Koch Inst, Dept Infect Dis, Mycot & Parasit Agents & Mycobacteria FG16, Berlin, Germany | - |
Descrição: dc.description | Univ Edinburgh, Inst Immunol & Infect Res, Edinburgh, Midlothian, Scotland | - |
Descrição: dc.description | Univ Glasgow, Wellcome Ctr Integrat Parasitol, Glasgow, Lanark, Scotland | - |
Descrição: dc.description | Robert Koch Inst, Metab Microbial Pathogens NG2, Berlin, Germany | - |
Descrição: dc.description | Univ Melbourne, Bio21 Mol Sci & Biotechnol Inst, Dept Biochem & Mol Biol, Parkville, Vic, Australia | - |
Descrição: dc.description | Univ Estadual Paulista, Inst Biociencias, Dept Parasitol, Botucatu, SP, Brazil | - |
Descrição: dc.description | Robert Koch Inst, Epidemiol Highly Pathogen Microorganisms, Berlin, Germany | - |
Descrição: dc.description | Robert Koch Inst, Prote & Spect ZBS 6, Berlin, Germany | - |
Descrição: dc.description | Leibniz Inst Mol Pharmacol, Dept NMR Supported Struct Biol, Berlin, Germany | - |
Descrição: dc.description | Univ Estadual Paulista, Inst Biociencias, Dept Parasitol, Botucatu, SP, Brazil | - |
Descrição: dc.description | Federal Ministry of Education and Research (BMBF): 01KI1715 | - |
Descrição: dc.description | European Commission Marie Curie Excellence grant: Ext-25435 | - |
Descrição: dc.description | Deutsche Forschungsgemeinschaft: AE16/5-1 | - |
Descrição: dc.description | Deutsche Forschungsgemeinschaft: AE16/5-2 | - |
Formato: dc.format | 19 | - |
Idioma: dc.language | en | - |
Publicador: dc.publisher | Amer Soc Microbiology | - |
Relação: dc.relation | Mbio | - |
???dc.source???: dc.source | Web of Science | - |
Palavras-chave: dc.subject | Kinetoplastida | - |
Palavras-chave: dc.subject | lateral gene transfer | - |
Palavras-chave: dc.subject | mitochondrial metabolism | - |
Palavras-chave: dc.subject | virulence factors | - |
Título: dc.title | Leishmania Encodes a Bacterium-like 2,4-Dienoyl-Coenzyme A Reductase That Is Required for Fatty Acid beta-Oxidation and Intracellular Parasite Survival | - |
Tipo de arquivo: dc.type | livro digital | - |
Aparece nas coleções: | Repositório Institucional - Unesp |
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