Antimalarial target vulnerability of the putative Plasmodium falciparum methionine synthase

被引：1

作者：

Leela, Nirut ^{[1
]}

Prommana, Parichat ^{[2
]}

Kamchonwongpaisan, Sumalee ^{[2
]}

Taechalertpaisarn, Tana ^{[1
]}

Shaw, Philip J. ^{[2
]}

机构：

[1] Mahidol Univ, Fac Sci, Dept Microbiol, Bangkok, Bangkok, Thailand

[2] Natl Sci & Technol Dev Agcy, Natl Ctr Genet Engn & Biotechnol BIOTEC, Pathum Thani, Thailand

来源：

PEERJ | 2024年 / 12卷

关键词：

Plasmodium falciparum; Methionine synthase; Malaria; GlmS riboswitch; GlmS ribozyme; Target vulnerability; DIHYDROFOLATE-REDUCTASE; PARASITE; METABOLISM; HYDROLASE;

D O I：

10.7717/peerj.16595

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Background. Plasmodium falciparum possesses a cobalamin-dependent methionine synthase (MS). MS is putatively encoded by the PF3D7_1233700 gene, which is orthologous and syntenic in Plasmodium. However, its vulnerability as an antimalarial target has not been assessed. Methods. We edited the PF3D7_1233700 and PF3D7_0417200 (dihydrofolate reductase-thymidylate synthase, DHFR-TS) genes and obtained transgenic P. falci-parum parasites expressing epitope-tagged target proteins under the control of the glmS ribozyme. Conditional loss-of-function mutants were obtained by treating transgenic parasites with glucosamine. Results. DHFR-TS, but not MS mutants showed a significant proliferation defect over 96 h, suggesting that P. falciparum MS is not a vulnerable antimalarial target.

引用

页数：17

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