Effect of fosmidomycin on metabolic and transcript profiles of the methylerythritol phosphate pathway in Plasmodium falciparum
Mem. Inst. Oswaldo Cruz
;
102(3): 377-384, June 2007. graf, tab
Artigo
em Inglês
| LILACS
| ID: lil-452518
ABSTRACT
In Plasmodium falciparum, the formation of isopentenyl diphosphate and dimethylallyl diphosphate, central intermediates in the biosynthesis of isoprenoids, occurs via the methylerythritol phosphate (MEP) pathway. Fosmidomycin is a specific inhibitor of the second enzyme of the MEP pathway, 1-deoxy-D-xylulose-5-phosphate reductoisomerase. We analyzed the effect of fosmidomycin on the levels of each intermediate and its metabolic requirement for the isoprenoid biosynthesis, such as dolichols and ubiquinones, throughout the intraerythrocytic cycle of P. falciparum. The steady-state RNA levels of the MEP pathway-associated genes were quantified by real-time polymerase chain reaction and correlated with the related metabolite levels. Our results indicate that MEP pathway metabolite peak precede maximum transcript abundance during the intraerythrocytic cycle. Fosmidomycin-treatment resulted in a decrease of the intermediate levels in the MEP pathway as well as in ubiquinone and dolichol biosynthesis. The MEP pathway associated transcripts were modestly altered by the drug, indicating that the parasite is not strongly responsive at the transcriptional level. This is the first study that compares the effect of fosmidomycin on the metabolic and transcript profiles in P. falciparum, which has only the MEP pathway for isoprenoid biosynthesis.
Texto completo:
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Índice:
LILACS (Américas)
Assunto principal:
Plasmodium falciparum
/
Fosfatos Açúcares
/
Eritritol
/
Eritrócitos
/
Fosfomicina
Limite:
Animais
Idioma:
Inglês
Revista:
Mem. Inst. Oswaldo Cruz
Assunto da revista:
Medicina Tropical
/
Parasitologia
Ano de publicação:
2007
Tipo de documento:
Artigo
/
Documento de projeto
País de afiliação:
Brasil
/
Estados Unidos
Instituição/País de afiliação:
NYU School of Medicine/US
/
Universidade de São Paulo/BR
/
Yeshiva University/US
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