Dominance of P-glycoprotein 12 in phenotypic resistance conversion against ivermectin in Caenorhabditis elegans

PloS One
Luiza Almeida FigueiredoRicardo Toshio Fujiwara

Abstract

While diseases caused by nematodes remains a considerable drawback for the livestock, agriculture and public health, anthelmintics drug resistance has been observed over the past years and is a major concern for parasite control. Ivermectin, initially considered as a highly potent drug, currently presents a reduced anti-helminthic efficacy, which is influenced by expression of several ATP-binding cassette transporters (ABC), among them the P-glycoproteins (Pgps). Here we present some evidences of Pgps dominance during Ivermectin resistance/susceptibility using Pgps double silencing in C. elegans and the phylogenetic relationship of Pgps among nematodes, which strengthen the use of this model for study of drug resistance in nematodes. Firstly, we evaluated the quantitative gene expression of 12 out the 15 known Pgps from resistant and WT strains of C. elegans, we demonstrated the upregulation of Pgps 12 and 13 and downregulation of all remaining Pgps in ivermectin resistant strain. By using an RNAi loss-of-function approach we observed that Pgp 12 gene silencing reverts the resistance phenotype to ivermectin, while Pgp 4 gene silencing does not alter the resistance phenotype but induces a resistance in wild type strain. Interest...Continue Reading

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Citations

Jun 20, 2019·Journal of Experimental & Clinical Cancer Research : CR·Lu JiangYi-Jun Wu
Aug 14, 2020·Scientific Reports·Alexander P GerhardGeorg von Samson-Himmelstjerna
Mar 28, 2019·Revista brasileira de parasitologia veterinária = Brazilian journal of veterinary parasitology : Órgão Oficial do Colégio Brasileiro de Parasitologia Veterinária·Dauana Mesquita SousaClaudia Maria Leal Bevilaqua
Jun 24, 2019·International Journal for Parasitology. Drugs and Drug Resistance·Roger K Prichard, Timothy G Geary
Feb 23, 2021·Journal of Toxicology and Environmental Health. Part B, Critical Reviews·Jessica H HartmanJoel N Meyer

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Methods Mentioned

BETA
PCR
MDS

Software Mentioned

R
7500
Primique
ClustalW
GE Image Quant TL
PHYLIP
GraphPad Prism

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Anthelmintics (ASM)

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.

Antiparasitics

Antiparasitics are medications which are indicated for the treatment of parasitic diseases. Discover the latest research on antiparasitics here.

Anthelmintics

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.