Skip to main content
SpringerLink
Log in

ABC transporters as a multidrug detoxification mechanism in Rhipicephalus (Boophilus) microplus

  • Original Paper
  • Published:
Parasitology Research Aims and scope Submit manuscript

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 % (LC50) 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 LC50 did not change in POA susceptible strain larvae. LC50 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Bain LJ, LeBlanc GA (1996) Interaction of structurally diverse pesticides with the human MDR1 gene product P-glycoprotein. Toxicol Appl Pharmacol 141:288–298

    PubMed  CAS  Google Scholar 

  • Benavides E, Rodríguez JL, Romero A (2000) Isolation and partial characterization of the Montecitos strain of Boophilus microplus (Canestrini, 1877) multiresistant to different acaricides. Ann NY Acad Sci 916:668–671

    Article  PubMed  CAS  Google Scholar 

  • Buss DS, McCaffery AR, Callaghan A (2002) Evidence for p-glycoprotein modification of insecticide toxicity in mosquitoes of the Culex pipiens complex. Med Vet Entomol 16:218–222

    Article  PubMed  CAS  Google Scholar 

  • Castro-Janer E, Martins JR, Mendes MC, Namindome A, Klafke GM, Schumaker TT (2010) Diagnoses of fipronil resistance in Brazilian cattle ticks (Rhipicephalus (Boophilus) microplus) using in vitro larval bioassays. Vet Parasitol 173:300–306

    Article  PubMed  CAS  Google Scholar 

  • Da Silva Vaz Jr I, Lermen TT, Michelon A, Ferreira CAS, de Freitas DRJ, Termignoni C, Masuda A (2004) Effect of acaricides on the activity of a Boophilus microplus glutathione S-transferase. Vet Parasitol 119:237–245

    Article  Google Scholar 

  • FAO (1984) Ticks and tick borne disease control. A practical field manual. Volume I. Tick control. Food and Agriculture Organization, Animal Production and Health Division, Rome, p 299

    Google Scholar 

  • FAO (2004) Resistance management and integrated parasite control in Ruminants—guidelines, executive summary. Food and Agriculture Organization, Animal Production and Health Division, Rome, p 11

    Google Scholar 

  • Fernández-Salas A, Rodríguez-Vivas RI, Alonso-Díaz MA (2012) First report of a Rhipicephalus microplus tick population multi-resistant to acaricides and ivermectin in the Mexican tropics. Vet Parasitol 183:338–342

    Article  PubMed  Google Scholar 

  • Ffrench-Constant RH, Daborn PJ, Le Goff G (2004) The genetics and genomics of insecticide resistance. Trends Genet 20:163–170

    Article  PubMed  CAS  Google Scholar 

  • Guerrero FD, Pruett JH, Li AY (2002) Molecular and biochemical diagnosis of esterase-mediated pyrethroid resistance in a Mexican strain of Boophilus microplus (Acari: Ixodidae). Exp Appl Acarol 28:257–264

    Article  PubMed  CAS  Google Scholar 

  • Guerrero FD, Lovis L, Martins JR (2012) Acaricide resistance mechanisms in Rhipicephalus (Boophilus) microplus. Rev Bras Parasitol Vet 21:1–6

    Article  PubMed  Google Scholar 

  • Holland IB, Blight MA (1999) ABC-ATPases, adaptable energy generators fuelling transmembrane movement of a variety of molecules in organisms from bacteria to humans. J Mol Biol 293:381–399

    Article  PubMed  CAS  Google Scholar 

  • Ishikawa T (1992) The ATP-dependent glutathione S-conjugate export pump. Trends Biochem Sci 17:463–468

    Article  PubMed  CAS  Google Scholar 

  • James CE, Davey MW (2009) Increased expression of ABC transport proteins is associated with ivermectin resistance in the model nematode Caenorhabditis elegans. Int J Parasitol 39:213–220

    Article  PubMed  CAS  Google Scholar 

  • Jonsson NN, Bock RE, Jorgensen WK (2008) Productivity and health effects of anaplasmosis and babesiosis on Bos indicus cattle and their crosses, and the effects of differing intensity of tick control in Australia. Vet Parasitol 155:1–9

    Article  PubMed  CAS  Google Scholar 

  • Kaminsky R, Bapst B, Stein PA, Strehlau GA, Allan BA, Hosking BC, Rolfe PF, Sager H (2011) Differences in efficacy of monepantel, derquantel and abamectin against multi-resistant nematodes of sheep. Parasitol Res 109:19–23

    Article  PubMed  Google Scholar 

  • Lage H (2003) ABC-transporters: implications on drug resistance from microorganisms to human cancers. Int J Antimicrob Agents 22:188–199

    Article  PubMed  CAS  Google Scholar 

  • Leslie EM, Deeley RG, Cole SP (2005) Multidrug resistance proteins: role of P-glycoprotein, MRP1, MRP2, and BCRP (ABCG2) in tissue defense. Toxicol Appl Pharmacol 204:216–237

    Article  PubMed  CAS  Google Scholar 

  • Lespine A, Alvinerie M, Vercruysse J, Prichard RK, Geldhof P (2008) ABC transporter modulation: a strategy to enhance the activity of macrocyclic lactone anthelmintics. Trends Parasitol 24:293–298

    Article  PubMed  CAS  Google Scholar 

  • Li AY, Davey RB, Miller RJ, Guerrero FD, George JE (2008) Genetics and mechanisms of permethrin resistance in the Santa Luiza strain of Boophilus microplus (Acari: Ixodidae). J Med Entomol 45:427–438

    Article  PubMed  CAS  Google Scholar 

  • Lifschitz A, Entrocasso C, Alvarez L, Lloberas M, Ballent M, Manazza G, Virkel G, Borda B, Lanusse C (2010) Interference with P-glycoprotein improves ivermectin activity against adult resistant nematodes in sheep. Vet Parasitol 172:291–298

    Article  PubMed  CAS  Google Scholar 

  • Martínez-Valladares M, Famularo MR, Fernández-Pato N, Cordero-Pérez C, Castañón-Ordóñez L, Rojo-Vázquez FA (2012) Characterization of a multidrug resistant Teladorsagia circumcincta isolate from Spain. Parasitol Res 110:2083–2087

    Article  PubMed  Google Scholar 

  • Martins JR, Furlong J (2001) Avermectin resistance of the cattle tick Boophilus microplus in Brazil. Vet Rec 149:64

    PubMed  CAS  Google Scholar 

  • Miller RJ, Davey RB, George JE (2002) Modification of the food and agriculture organisation larval packet test to measure amitraz susceptibility against ixodidae. J Med Entomol 39:645–651

    Article  PubMed  Google Scholar 

  • Mounsey KE, Pasay CJ, Arlian LG, Morgan MS, Holt DC, Currie BJ, Walton SF, McCarthy JS (2010) Increased transcription of glutathione S-transferases in acaricide exposed scabies mites. Parasit Vectors 18:3–43

    Google Scholar 

  • Nolan J, Wilson JT, Green PE, Bird PE (1989) Synthetic pyrethroid resistance in field samples in the cattle tick (Boophilus microplus). Aust Vet J 66:179–182

    Article  PubMed  CAS  Google Scholar 

  • Ortiz EM, Santamaría VM, Ortiz NA, Soberanes CN, Osorio MJ, Franco BR, Martínez IF, Quezada DR, Fragoso SH (1995) Caracterización of Boophilus microplus resistance to ixodicides in México. In: Seminario internacional de Parasitología Animal. Acapulco, México, 58–66

  • Patarroyo JH, Costa JO (1980) Susceptibility of Brazilian samples of Boophilus microplus to organophosphorus acaricides. Trop Anim Health Prod 12:6–10

    Article  PubMed  CAS  Google Scholar 

  • Perry T, Batterham P, Daborn PJ (2011) The biology of insecticidal activity and resistance. Insect Biochem Mol Biol 41:411–422

    Article  PubMed  CAS  Google Scholar 

  • Pohl PC, Klafke GM, Carvalho DD, Martins JR, Daffre S, da Silva Vaz Jr I, Masuda A (2011) ABC transporter efflux pumps: a defense mechanism against ivermectin in Rhipicephalus (Boophilus) microplus. Int J Parasit 41:1323–1333

    Article  CAS  Google Scholar 

  • Porretta D, Gargani M, Bellini R, Medici A, Punelli F, Urbanelli S (2008) Defence mechanisms against insecticides temephos and diflubenzuron in the mosquito Aedes caspius: the P-glycoprotein efflux pumps. Med Vet Entomol 22:48–54

    Article  PubMed  CAS  Google Scholar 

  • Robertson J.R., Preisler H.K., Russell R.M., Plus Polo., (2002) Probit and Logit Analysis User’s Guide. LeOra Software, Petaluna, CA

  • Rosario-Cruz R, Almazan C, Miller RJ, Dominguez-Garcia DI, Hernandez-Ortiz R, de la Fuente J (2009a) Genetic basis and impact of tick acaricide resistance. Front Biosci 14:2657–2665

    Article  PubMed  CAS  Google Scholar 

  • Rosario-Cruz R, Guerrero FD, Miller RJ, Rodriguez-Vivas RI, Tijerina M, Dominguez-Garcia DI, Hernandez-Ortiz R, Cornel AJ, McAbee RD, Alonso-Diaz MA (2009b) Molecular survey of pyrethroid resistance mechanisms in Mexican field populations of Rhipicephalus (Boophilus) microplus. Parasitol Res 105:1145–1153

    Article  PubMed  Google Scholar 

  • Soberanes CN, Santamaría VM, Fragoso SH, García VZ (2002) Primer caso de resistencia al amitraz en la garrapata del ganado Boophilus microplus en México. Tec Pec Mex 40:81–92

    Google Scholar 

  • Tompkins JB, Stitt LE, Morrissette AM, Ardelli BF (2011) The role of Brugia malayi ATP-binding cassette (ABC) transporters in potentiating drug sensitivity. Parasitol Res 109:1311–1322

    Article  PubMed  Google Scholar 

  • Xu M, Molento M, Blackhall W, Ribeiro P, Beech R, Prichard R (1998) Ivermectin resistance in nematodes may be caused by alteration of P-glycoprotein homolog. Mol Biochem Parasitol 91:327–335

    Article  PubMed  CAS  Google Scholar 

  • Yoon KS, Strycharz JP, Baek JH, Sun W, Kim JH, Kang JS, Pittendrigh BR, Lee SH, Clark JM (2011) Brief exposures of human body lice to sublethal amounts of ivermectin over-transcribes detoxification genes involved in tolerance. Insect Mol Biol 20:687–699

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

We thank the CNPq—Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular, FINEP, CAPES, CNPq and FAPERGS for supporting our work.

Author information

Authors and Affiliations

  1. Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Avenida Bento Gonçalves, 9500, Prédio 43421, Porto Alegre, RS, 91501-970, Brazil

    Paula C. Pohl, Itabajara da Silva Vaz Jr & Aoi Masuda

  2. Instituto de Pesquisas Veterinárias Desidério Finamor- FEPAGRO, BR 116, Km 291, Estrada do Conde, 6000, Eldorado do Sul, RS, 92900-000, Brazil

    Guilherme M. Klafke, José Reck Júnior & João Ricardo Martins

  3. Faculdade de Veterinária, Universidade Federal do Rio Grande do Sul, Avenida Bento Gonçalves, 9090, Porto Alegre, RS, 91540-000, Brazil

    Itabajara da Silva Vaz Jr

  4. Departamento de Biologia Molecular e Biotecnologia, Universidade Federal do Rio Grande do Sul, Avenida Bento Gonçalves, 9500, Prédio 43421, Porto Alegre, RS, 91501-970, Brazil

    Aoi Masuda

Authors
  1. Paula C. Pohl
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Guilherme M. Klafke
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. José Reck Júnior
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. João Ricardo Martins
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Itabajara da Silva Vaz Jr
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Aoi Masuda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Itabajara da Silva Vaz Jr.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supporting Fig. 1

Effect of CsA and MK571 (15 μM) on mortality of susceptible (POA) R. microplus larvae to acaricides determined by LPT, as described in Fig. 1 (PDF 94 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pohl, P.C., Klafke, G.M., Júnior, J.R. et al. ABC transporters as a multidrug detoxification mechanism in Rhipicephalus (Boophilus) microplus . Parasitol Res 111, 2345–2351 (2012). https://doi.org/10.1007/s00436-012-3089-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00436-012-3089-1

Keywords

Search

Navigation