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Characterisation of P-glycoprotein-9.1 in Haemonchus contortus

Overview of attention for article published in Parasites & Vectors, January 2016
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Title
Characterisation of P-glycoprotein-9.1 in Haemonchus contortus
Published in
Parasites & Vectors, January 2016
DOI 10.1186/s13071-016-1317-8
Pubmed ID
Authors

Pablo Godoy, Hua Che, Robin N. Beech, Roger K. Prichard

Abstract

The existence nematodes of veterinary importance such as Haemonchus contortus resistant to anthelmintic drugs, including the macrocyclic lactones, has become a major concern in animal health. Macrocyclic lactone resistance in H. contortus seems to be multigenic including the active efflux of these drugs by P-glycoproteins, members of the ABC transporter family, present in this parasite. The goals of the present work were to determine the activity of H. contortus P-glycoprotein 9.1 (Hco-PGP-9.1) and its interaction with the avermectins, ivermectin, abamectin, and also the milbemycin, moxidectin. Additionally, the localisation of Hco-PGP-9.1 was sought in adult worms. Hco-Pgp-9.1 was cloned and expressed in mammalian cells and its expression profile was determined at the transcriptional and protein level by qRT-PCR and Western-blot, respectively. The nematode transport activity was assessed using the tracer dye Rhodamine 123. A ligand competition assay between different macrocyclic lactones and Rhodamine 123 was used to establish whether or not there was interaction between Hco-PGP-9.1 and the avermectins (abamectin and ivermectin) or moxidectin. In addition, immunostaining was carried out to localise Hco-PGP-9.1 expression in the transgenic cells and in adult female parasites. Hco-PGP-9.1 was expressed in the cell membrane of the transfected host cells and was able to extrude Rhodamine 123. Ivermectin and abamectin, but not moxidectin, had a pronounced inhibitory effect on the ability of Hco-PGP-9.1 to transport Rhodamine 123. Antibodies raised against Hco-PGP-9.1 epitopes localised to the uterus of adult female H. contortus. These results suggest a strong interaction of the avermectins with Hco-PGP-9.1. However, possibly due to its physico-chemical properties, moxidectin had markedly less effect on Hco-PGP-9.1. Because of the greater interaction of the avermectins than moxidectin with this transporter, it is more likely to contribute to avermectin resistance than to moxidectin resistance in H. contortus. Possible over expression of Hco-PGP-9.1 in the female reproductive system in resistant worms could reduce paralysis of the uterus by macrocyclic lactones, allowing continued egg release in drug challenged resistant worms.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 39 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Brazil 1 3%
Unknown 38 97%

Demographic breakdown

Readers by professional status Count As %
Researcher 10 26%
Student > Master 5 13%
Student > Doctoral Student 4 10%
Student > Ph. D. Student 3 8%
Student > Postgraduate 3 8%
Other 6 15%
Unknown 8 21%
Readers by discipline Count As %
Agricultural and Biological Sciences 13 33%
Veterinary Science and Veterinary Medicine 7 18%
Biochemistry, Genetics and Molecular Biology 4 10%
Chemistry 2 5%
Nursing and Health Professions 1 3%
Other 3 8%
Unknown 9 23%
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 30 January 2016.
All research outputs
#13,455,370
of 22,842,950 outputs
Outputs from Parasites & Vectors
#2,457
of 5,467 outputs
Outputs of similar age
#191,225
of 396,721 outputs
Outputs of similar age from Parasites & Vectors
#73
of 166 outputs
Altmetric has tracked 22,842,950 research outputs across all sources so far. This one is in the 39th percentile – i.e., 39% of other outputs scored the same or lower than it.
So far Altmetric has tracked 5,467 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.7. This one has gotten more attention than average, scoring higher than 52% of its peers.
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 396,721 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 50% of its contemporaries.
We're also able to compare this research output to 166 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 53% of its contemporaries.