title: ABC transporters as a multidrug detoxification mechanism in Rhipicephalus (Boophilus) microplus.
abstract: ATP-binding cassette (ABC) transporters are responsible for pumping drugs across membranes and are an important drug detoxification mechanism. Since ABC transporters act on a wide spectrum of chemical compounds, they have been associated with multidrug resistance phenotype in various parasites and cancer cells. Here, we document the presence of a Rhipicephalus (Boophilus) microplus tick population (Jaguar) resistant to four acaricide classes (organophosphates (OP), synthetic pyrethroids (SP), amitraz and macrocyclic lactones (ML)) and reveal that the cattle tick has a multidrug detoxification mechanism based on ABC transporter proteins. Acaricide toxicity was assessed using the larval packet test (LPT), and mortality data were subjected to probit analysis using a susceptible strain (POA) as reference. Larvae were pre-exposed to sub-lethal doses of the ABC-transporter inhibitors, cyclosporin A (CsA) and MK571, and subsequently treated with ivermectin, abamectin, moxidectin, chlorpyriphos, cypermethrin, or amitraz in LPT. Results show that lethal concentrations 50 % (LC(50)) of ivermectin, abamectin, moxidectin (MLs), and chlorpyriphos (OP) were significantly reduced in larvae exposed to CsA and MK571 inhibitors in the Jaguar resistant population, but LC(50) did not change in POA susceptible strain larvae. LC(50) of cypermetrin (SP) and amitraz remained unchanged in inhibitor-exposed larvae, compared to larvae from Jaguar and POA strains not exposed to inhibitor. These results suggest that ABC transporter proteins can protect ticks against a wide range of acaricides and have an important implication in drug resistance development as a multidrug detoxification mechanism.
authors.affiliation: Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Avenida Bento Gonçalves, 9500 Prédio 43421, Porto Alegre, RS 91501-970, Brazil.
authors.forename: Paula C
authors.initials: PC
authors.lastname: Pohl
authors.forename: Guilherme M
authors.initials: GM
authors.lastname: Klafke
authors.forename: José Reck
authors.initials: JR
authors.lastname: Júnior
authors.forename: João Ricardo
authors.initials: JR
authors.lastname: Martins
authors.forename: Itabajara
authors.initials: I
authors.lastname: da Silva Vaz
authors.forename: Aoi
authors.initials: A
authors.lastname: Masuda
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D056810:Acaricides / Q000378:metabolism*; D000818:Animals; D001681:Biological Assay; D004351:Drug Resistance; D007814:Larva / Q000187:drug effects; D047028:Macrocyclic Compounds / Q000378:metabolism; D010755:Organophosphates / Q000378:metabolism; D046009:Panthera / Q000469:parasitology; D011722:Pyrethrins / Q000378:metabolism; D048494:Rhipicephalus / Q000187:drug effects* / Q000201:enzymology*; D016019:Survival Analysis
chemical_list: D018528:ATP-Binding Cassette Transporters; D056810:Acaricides; D047028:Macrocyclic Compounds; D010755:Organophosphates; D011722:Pyrethrins