Analysis and partial reversal of multidrug resistance to anthelmintics due to P-glycoprotein in Haemonchus contortus eggs using Lens culinaris lectin.
Our previous work has shown that drug efflux pumps close to MDR1 P-glycoprotein (Pgp) can regulate anthelmintic efflux in nematodes in a way similar to that of the mutidrug resistance system (MDR) in vertebrate cancer cells. In the present study, the role of the glycosylation of Pgp was studied using a lectin specific for the alpha-mannosyl residues ( Lens culinaris agglutinin, LCA). Highly significant reversion (up to 50%) in the resistance to thiabendazole of eggs pre-treated with the lectin was obtained. Flow cytometric examinations were performed using FITC-labelled lectin. The results demonstrated that: (1) the number of Pgp sites was higher in resistant H aemonchus contortus, (2) resistance can also be associated with a decreased affinity of LCA for these sites, (3) eggs stained with LCA were also stained with specific MDR1 monoclonal antibodies. The implication of the glycosylation of Pgp in the activity and/or degradation of these pumps in eukaryotic cells is discussed.
Kerboeuf
D
D
INRA, Bioaggressors, Health and Environment, 37380 Nouzilly, France. kerboeuf@tours.inra.fr
Guégnard
F
F
Le Vern
Y
Y
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D006188:Haemonchiasis / Q000188:drug therapy; D006189:Haemonchus / Q000187:drug effects* / Q000254:growth & development; D008358:Mannose / Q000737:chemistry; D010063:Ovum / Q000187:drug effects; D010270:Parasite Egg Count; D021261:Parasitic Sensitivity Tests; D037121:Plant Lectins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013045:Species Specificity; D013827:Thiabendazole / Q000494:pharmacology* / Q000627:therapeutic use
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000871:Anthelmintics; D037121:Plant Lectins; C033619:lentil lectin; D013827:Thiabendazole; D008358:Mannose