Anthelmintic resistance: markers for resistance, or susceptibility?
The Consortium for Anthelmintic Resistance and Susceptibility (CARS) brings together researchers worldwide, with a focus of advancing knowledge of resistance and providing information on detection methods and treatment strategies. Advances in this field suggest mechanisms and features of resistance that are shared among different classes of anthelmintic. Benzimidazole resistance is characterized by specific amino acid substitutions in beta-tubulin. If present, these substitutions increase in frequency upon drug treatment and lead to treatment failure. In the laboratory, sequence substitutions in ion-channels can contribute to macrocyclic lactone resistance, but there is little evidence that they are significant in the field. Changes in gene expression are associated with resistance to several different classes of anthelmintic. Increased P-glycoprotein expression may prevent drug access to its site of action. Decreased expression of ion-channel subunits and the loss of specific receptors may remove the drug target. Tools for the identification and genetic analysis of parasitic nematodes and a new online database will help to coordinate research efforts in this area. Resistance may result from a loss of sensitivity as well as the appearance of resistance. A focus on the presence of anthelmintic susceptibility may be as important as the detection of resistance.
Beech
R N
RN
Institute of Parasitology, Macdonald College, McGill University, Ste Anne de Bellevue, QC H9X3V9, Canada. robin.beech@mcgill.ca
Skuce
P
P
Bartley
D J
DJ
Martin
R J
RJ
Prichard
R K
RK
Gilleard
J S
JS
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D019943:Amino Acid Substitution; D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology; D015415:Biomarkers; D018680:Cholinergic Antagonists / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006376:Helminths / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D058446:Ligand-Gated Ion Channels / Q000235:genetics / Q000378:metabolism; D047028:Macrocyclic Compounds / Q000494:pharmacology; D008297:Male; D021261:Parasitic Sensitivity Tests; D014404:Tubulin / Q000235:genetics* / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000871:Anthelmintics; D001562:Benzimidazoles; D015415:Biomarkers; D018680:Cholinergic Antagonists; D058446:Ligand-Gated Ion Channels; D047028:Macrocyclic Compounds; D014404:Tubulin
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