Suppression of experimental cerebral malaria by disruption of malate:quinone oxidoreductase
Abstract Background Aspartate, which is converted from oxaloacetate (OAA) by aspartate aminotransferase, is considered an important precursor for purine salvage and pyrimidine de novo biosynthesis, and is thus indispensable for the growth of Plasmodium parasites at the asexual blood stages. OAA can...
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ftdoajarticles:oai:doaj.org/article:b507927d51064b0c89c72f222a9a43af 2023-05-15T15:14:27+02:00 Suppression of experimental cerebral malaria by disruption of malate:quinone oxidoreductase Mamoru Niikura Keisuke Komatsuya Shin-Ichi Inoue Risa Matsuda Hiroko Asahi Daniel Ken Inaoka Kiyoshi Kita Fumie Kobayashi 2017-06-01T00:00:00Z https://doi.org/10.1186/s12936-017-1898-5 https://doaj.org/article/b507927d51064b0c89c72f222a9a43af EN eng BMC http://link.springer.com/article/10.1186/s12936-017-1898-5 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-017-1898-5 1475-2875 https://doaj.org/article/b507927d51064b0c89c72f222a9a43af Malaria Journal, Vol 16, Iss 1, Pp 1-11 (2017) Plasmodium berghei Fumarate hydratase (FH) Malate:quinone oxidoreductase (MQO) Luciferase–luciferin system Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2017 ftdoajarticles https://doi.org/10.1186/s12936-017-1898-5 2022-12-30T22:57:13Z Abstract Background Aspartate, which is converted from oxaloacetate (OAA) by aspartate aminotransferase, is considered an important precursor for purine salvage and pyrimidine de novo biosynthesis, and is thus indispensable for the growth of Plasmodium parasites at the asexual blood stages. OAA can be produced in malaria parasites via two routes: (i) from phosphoenolpyruvate (PEP) by phosphoenolpyruvate carboxylase (PEPC) in the cytosol, or (ii) from fumarate by consecutive reactions catalyzed by fumarate hydratase (FH) and malate:quinone oxidoreductase (MQO) in the mitochondria of malaria parasites. Although PEPC-deficient Plasmodium falciparum and Plasmodium berghei (rodent malaria) parasites show a growth defect, the mutant P. berghei can still cause experimental cerebral malaria (ECM) with similar dynamics to wild-type parasites. In contrast, the importance of FH and MQO for parasite viability, growth and virulence is not fully understood because no FH- and MQO-deficient P. falciparum has been established. In this study, the role of FH and MQO in the pathogenicity of asexual-blood-stage Plasmodium parasites causing cerebral malaria was examined. Results First, FH- and MQO-deficient parasites were generated by inserting a luciferase-expressing cassette into the fh and mqo loci in the genome of P. berghei ANKA strain. Second, the viability of FH-deficient and MQO-deficient parasites that express luciferase was determined by measuring luciferase activity, and the effect of FH or MQO deficiency on the development of ECM was examined. While the viability of FH-deficient P. berghei was comparable to that of control parasites, MQO-deficient parasites exhibited considerably reduced viability. FH activity derived from erythrocytes was also detected. This result and the absence of phenotype in FH-deficient P. berghei parasites suggest that fumarate can be metabolized to malate by host or parasite FH in P. berghei-infected erythrocytes. Furthermore, although the growth of FH- and MQO-deficient parasites was impaired, ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 16 1 |
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topic |
Plasmodium berghei Fumarate hydratase (FH) Malate:quinone oxidoreductase (MQO) Luciferase–luciferin system Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
spellingShingle |
Plasmodium berghei Fumarate hydratase (FH) Malate:quinone oxidoreductase (MQO) Luciferase–luciferin system Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Mamoru Niikura Keisuke Komatsuya Shin-Ichi Inoue Risa Matsuda Hiroko Asahi Daniel Ken Inaoka Kiyoshi Kita Fumie Kobayashi Suppression of experimental cerebral malaria by disruption of malate:quinone oxidoreductase |
topic_facet |
Plasmodium berghei Fumarate hydratase (FH) Malate:quinone oxidoreductase (MQO) Luciferase–luciferin system Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Aspartate, which is converted from oxaloacetate (OAA) by aspartate aminotransferase, is considered an important precursor for purine salvage and pyrimidine de novo biosynthesis, and is thus indispensable for the growth of Plasmodium parasites at the asexual blood stages. OAA can be produced in malaria parasites via two routes: (i) from phosphoenolpyruvate (PEP) by phosphoenolpyruvate carboxylase (PEPC) in the cytosol, or (ii) from fumarate by consecutive reactions catalyzed by fumarate hydratase (FH) and malate:quinone oxidoreductase (MQO) in the mitochondria of malaria parasites. Although PEPC-deficient Plasmodium falciparum and Plasmodium berghei (rodent malaria) parasites show a growth defect, the mutant P. berghei can still cause experimental cerebral malaria (ECM) with similar dynamics to wild-type parasites. In contrast, the importance of FH and MQO for parasite viability, growth and virulence is not fully understood because no FH- and MQO-deficient P. falciparum has been established. In this study, the role of FH and MQO in the pathogenicity of asexual-blood-stage Plasmodium parasites causing cerebral malaria was examined. Results First, FH- and MQO-deficient parasites were generated by inserting a luciferase-expressing cassette into the fh and mqo loci in the genome of P. berghei ANKA strain. Second, the viability of FH-deficient and MQO-deficient parasites that express luciferase was determined by measuring luciferase activity, and the effect of FH or MQO deficiency on the development of ECM was examined. While the viability of FH-deficient P. berghei was comparable to that of control parasites, MQO-deficient parasites exhibited considerably reduced viability. FH activity derived from erythrocytes was also detected. This result and the absence of phenotype in FH-deficient P. berghei parasites suggest that fumarate can be metabolized to malate by host or parasite FH in P. berghei-infected erythrocytes. Furthermore, although the growth of FH- and MQO-deficient parasites was impaired, ... |
format |
Article in Journal/Newspaper |
author |
Mamoru Niikura Keisuke Komatsuya Shin-Ichi Inoue Risa Matsuda Hiroko Asahi Daniel Ken Inaoka Kiyoshi Kita Fumie Kobayashi |
author_facet |
Mamoru Niikura Keisuke Komatsuya Shin-Ichi Inoue Risa Matsuda Hiroko Asahi Daniel Ken Inaoka Kiyoshi Kita Fumie Kobayashi |
author_sort |
Mamoru Niikura |
title |
Suppression of experimental cerebral malaria by disruption of malate:quinone oxidoreductase |
title_short |
Suppression of experimental cerebral malaria by disruption of malate:quinone oxidoreductase |
title_full |
Suppression of experimental cerebral malaria by disruption of malate:quinone oxidoreductase |
title_fullStr |
Suppression of experimental cerebral malaria by disruption of malate:quinone oxidoreductase |
title_full_unstemmed |
Suppression of experimental cerebral malaria by disruption of malate:quinone oxidoreductase |
title_sort |
suppression of experimental cerebral malaria by disruption of malate:quinone oxidoreductase |
publisher |
BMC |
publishDate |
2017 |
url |
https://doi.org/10.1186/s12936-017-1898-5 https://doaj.org/article/b507927d51064b0c89c72f222a9a43af |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 16, Iss 1, Pp 1-11 (2017) |
op_relation |
http://link.springer.com/article/10.1186/s12936-017-1898-5 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-017-1898-5 1475-2875 https://doaj.org/article/b507927d51064b0c89c72f222a9a43af |
op_doi |
https://doi.org/10.1186/s12936-017-1898-5 |
container_title |
Malaria Journal |
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16 |
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1766344900299718656 |