ArticleParasites & vectors2018
The MEP pathway in Babesia orientalis apicoplast, a potential target for anti-babesiosis drug development.
Article in Parasites & vectors, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.
- Targeting piroplasmosis and theileriosis: New frontiers in drug development.Tropical animal health and production · 2025Pooled it
- Comparative chemical genomics inProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Over 40 Years of Fosmidomycin Drug Research: A Comprehensive Review and Future Opportunities.Pharmaceuticals (Basel, Switzerland) · 2022Review
- The Biomedical Importance of the Missing Pathway for Farnesol and Geranylgeraniol Salvage.Molecules (Basel, Switzerland) · 2022Review
- YdfD, a Lysis Protein of the Qin Prophage, Is a Specific Inhibitor of the IspG-Catalyzed Step in the MEP Pathway ofInternational journal of molecular sciences · 2022Article
- Article
- Erythrocyte Adhesion of Merozoite Surface Antigen 2c1 Expressed During Extracellular Stages ofFrontiers in immunology · 2021Article
- Inhibitory Effects of Fosmidomycin AgainstFrontiers in cell and developmental biology · 2020Article
- Construction and Use of TransposonFrontiers in microbiology · 2019Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
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Abstract
backgroundThe apicomplexan parasite Babesia orientalis, the causative agent of water buffalo babesiosis in China, is widespread in central and south China, resulting in a huge economic loss annually. Currently, there is no effective vaccine or drug against this disease. Babesia bovis and Plasmodium falciparum were reported to possess an apicoplast which contains the methylerythritol phosphate (MEP) pathway inhibitable by fosmidomycin, suggesting that the pathway could serve as a drug target for screening new drugs. However, it remains unknown in B. orientalis.
methodsPrimers were designed according to the seven MEP pathway genes of Babesia microti and Babesia bovis. The genes were cloned, sequenced and analyzed. The open reading frames (ORFs) of the first two enzyme genes, 1-deoxy-D-xylulose 5-phosphate synthase (BoDXS) and 1-Deoxy-D-xylulose 5-phosphate reductoisomerase (BoDXR), were cloned into the pET-32a expression vector and expressed as a Trx-tag fusion protein. Rabbit anti-rBoDXS and rabbit anti-rBoDXR antibodies were generated. Western blot was performed to identify the native proteins of BoDXS and BoDXR in B. orientalis. Fosmidomycin and geranylgeraniol were used for inhibition assay and rescue assay, respectively, in the in vitro cultivation of B. orientalis.
resultsThe seven enzyme genes of the B. orientalis MEP pathway (DXS, DXR, IspD, IspE, IspF, IspG and IspH) were cloned and sequenced, with a full length of 2094, 1554, 1344, 1521, 654, 1932 and 1056 bp, respectively. BoDXS and BoDXR were expressed as Trx-tag fusion proteins, with a size of 95 and 67 kDa, respectively. Western blot identified a 77 kDa band for the native BoDXS and a 49 kDa band for the native BoDXR. The drug assay results showed that fosmidomycin could inhibit the growth of B. orientalis, and geranylgeraniol could reverse the effect of fosmidomycin.
conclusionsBabesia orientalis has the isoprenoid biosynthesis pathway, which could be a potential drug target for controlling and curing babesiosis. Considering the high price and instability of fosmidomycin, further studies should focus on the screening of stable and cheap drugs.
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