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RNA interference mediated knockdown of Brugia malayi UDP-Galactopyranose mutase severely affects parasite viability, embryogenesis and in vivo development of infective larvae

Overview of attention for article published in Parasites & Vectors, January 2017
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Title
RNA interference mediated knockdown of Brugia malayi UDP-Galactopyranose mutase severely affects parasite viability, embryogenesis and in vivo development of infective larvae
Published in
Parasites & Vectors, January 2017
DOI 10.1186/s13071-017-1967-1
Pubmed ID
Authors

Sweta Misra, Jyoti Gupta, Shailja Misra-Bhattacharya

Abstract

Galactofuranose is an essential cell surface component present in bacteria, fungi and several nematodes such as Caenorhabditis spp., Brugia spp., Onchocerca spp. and Strongyloides spp. This sugar maintains the integrity of parasite surface and is essential for virulence. UDP-Galactopyranose mutase (bmugm) plays a key role in Galf biosynthesis by catalyzing conversion of UDP-Galactopyranose into UDP-galactofuranose and knockout studies of the gene in Leishmania major, Mycobacterium and Aspergillus fumigatus displayed attenuated virulence while RNA interference study in C. elegans exhibited detrimental effects. Presence of UGM in several prokaryotic and eukaryotic microbial pathogens and its absence in higher eukaryotes renders it an attractive drug target. In the present study, RNA interference studies have been carried out to validate bmugm as an antifilarial drug target. RNA interference studies using two different sequences of siRNAs targeting bmugm were carried out. The in vitro gene silencing of adult B. malayi parasites was undertaken to observe the effects on parasites. Infective larvae were also exposed to siRNAs and their in vivo development in jirds was observed. The in vitro gene silencing induced by siRNA1 and 2 individually as well as together knocked down the bmugm gene expression causing impaired viability of the exposed worms along with extremely reduced motility, abridged microfilarial release and adversely effected embryogenesis. The combinatorial in vitro gene silencing revealed marginally better results than both the siRNAs individually. Thus, infective larvae were treated with siRNA combination which showed downregulation of bmugm mRNA expression resulting into sluggish larval movements and/or death. The siRNA-treated actively motile larvae when inoculated intraperitoneally into jirds demonstrated highly reduced transformation of these larvae into adult worms with detrimental effects on embryogenesis. The effects of gene silencing were long-lasting as the adult worms developed from siRNA-treated larvae showed noticeable knockdown in the target gene expression. The validation studies undertaken here conclude that bmugm is essential for the proper development and survival of the parasite and support its candidature as an antifilarial drug target.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 41 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 41 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 7 17%
Student > Ph. D. Student 6 15%
Student > Master 4 10%
Other 3 7%
Student > Postgraduate 3 7%
Other 9 22%
Unknown 9 22%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 12 29%
Medicine and Dentistry 6 15%
Agricultural and Biological Sciences 5 12%
Immunology and Microbiology 2 5%
Business, Management and Accounting 1 2%
Other 2 5%
Unknown 13 32%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 10 January 2018.
All research outputs
#14,908,193
of 22,940,083 outputs
Outputs from Parasites & Vectors
#3,095
of 5,482 outputs
Outputs of similar age
#240,936
of 417,650 outputs
Outputs of similar age from Parasites & Vectors
#47
of 117 outputs
Altmetric has tracked 22,940,083 research outputs across all sources so far. This one is in the 32nd percentile – i.e., 32% of other outputs scored the same or lower than it.
So far Altmetric has tracked 5,482 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 38th percentile – i.e., 38% 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 417,650 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 39th percentile – i.e., 39% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 117 others from the same source and published within six weeks on either side of this one. This one is in the 47th percentile – i.e., 47% of its contemporaries scored the same or lower than it.