Effect of fosmidomycin on metabolic and transcript profiles of the methylerythritol phosphate pathway in Plasmodium falciparum
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...
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| Format: | Article |
| Language: | English |
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Fundação Oswaldo Cruz (FIOCRUZ)
2007-06-01
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| Series: | Memorias do Instituto Oswaldo Cruz |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762007000300019 |
| _version_ | 1797757062782910464 |
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| author | María B Cassera Emilio F Merino Valnice J Peres Emilia A Kimura Gerhard Wunderlich Alejandro M Katzin |
| author_facet | María B Cassera Emilio F Merino Valnice J Peres Emilia A Kimura Gerhard Wunderlich Alejandro M Katzin |
| author_sort | María B Cassera |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T18:10:37Z |
| format | Article |
| id | doaj.art-b7f069bcfde046a0946a99f0f209621b |
| institution | Directory Open Access Journal |
| issn | 0074-0276 1678-8060 |
| language | English |
| last_indexed | 2024-03-12T18:10:37Z |
| publishDate | 2007-06-01 |
| publisher | Fundação Oswaldo Cruz (FIOCRUZ) |
| record_format | Article |
| series | Memorias do Instituto Oswaldo Cruz |
| spelling | doaj.art-b7f069bcfde046a0946a99f0f209621b2023-08-02T09:16:22ZengFundação Oswaldo Cruz (FIOCRUZ)Memorias do Instituto Oswaldo Cruz0074-02761678-80602007-06-011023377384Effect of fosmidomycin on metabolic and transcript profiles of the methylerythritol phosphate pathway in Plasmodium falciparumMaría B CasseraEmilio F MerinoValnice J PeresEmilia A KimuraGerhard WunderlichAlejandro M KatzinIn 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.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762007000300019Plasmodium falciparummalariafosmidomycinisoprenoid biosynthesisreal time polymerase chain reaction |
| spellingShingle | María B Cassera Emilio F Merino Valnice J Peres Emilia A Kimura Gerhard Wunderlich Alejandro M Katzin Effect of fosmidomycin on metabolic and transcript profiles of the methylerythritol phosphate pathway in Plasmodium falciparum Memorias do Instituto Oswaldo Cruz Plasmodium falciparum malaria fosmidomycin isoprenoid biosynthesis real time polymerase chain reaction |
| title | Effect of fosmidomycin on metabolic and transcript profiles of the methylerythritol phosphate pathway in Plasmodium falciparum |
| title_full | Effect of fosmidomycin on metabolic and transcript profiles of the methylerythritol phosphate pathway in Plasmodium falciparum |
| title_fullStr | Effect of fosmidomycin on metabolic and transcript profiles of the methylerythritol phosphate pathway in Plasmodium falciparum |
| title_full_unstemmed | Effect of fosmidomycin on metabolic and transcript profiles of the methylerythritol phosphate pathway in Plasmodium falciparum |
| title_short | Effect of fosmidomycin on metabolic and transcript profiles of the methylerythritol phosphate pathway in Plasmodium falciparum |
| title_sort | effect of fosmidomycin on metabolic and transcript profiles of the methylerythritol phosphate pathway in plasmodium falciparum |
| topic | Plasmodium falciparum malaria fosmidomycin isoprenoid biosynthesis real time polymerase chain reaction |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762007000300019 |
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