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The MEP pathway in Babesia orientalis apicoplast, a potential target for anti-babesiosis drug development

Overview of attention for article published in Parasites & Vectors, August 2018
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Title
The MEP pathway in Babesia orientalis apicoplast, a potential target for anti-babesiosis drug development
Published in
Parasites & Vectors, August 2018
DOI 10.1186/s13071-018-3038-7
Pubmed ID
Authors

Lan He, Pei He, Xiaoying Luo, Muxiao Li, Long Yu, Jiaying Guo, Xueyan Zhan, Guan Zhu, Junlong Zhao

Abstract

The 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. Primers 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. The 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. Babesia 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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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 24 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 24 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 4 17%
Student > Doctoral Student 3 13%
Student > Master 3 13%
Student > Bachelor 2 8%
Researcher 2 8%
Other 2 8%
Unknown 8 33%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 5 21%
Chemistry 3 13%
Agricultural and Biological Sciences 2 8%
Pharmacology, Toxicology and Pharmaceutical Science 1 4%
Computer Science 1 4%
Other 3 13%
Unknown 9 38%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 August 2018.
All research outputs
#18,646,262
of 23,099,576 outputs
Outputs from Parasites & Vectors
#4,275
of 5,522 outputs
Outputs of similar age
#254,326
of 330,726 outputs
Outputs of similar age from Parasites & Vectors
#114
of 148 outputs
Altmetric has tracked 23,099,576 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 5,522 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.7. This one is in the 11th percentile – i.e., 11% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 330,726 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 12th percentile – i.e., 12% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 148 others from the same source and published within six weeks on either side of this one. This one is in the 10th percentile – i.e., 10% of its contemporaries scored the same or lower than it.