{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T15:53:35Z","timestamp":1793894015681,"version":"4.8.0"},"reference-count":57,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,8,17]],"date-time":"2018-08-17T00:00:00Z","timestamp":1534464000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,8,17]],"date-time":"2018-08-17T00:00:00Z","timestamp":1534464000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The cattle tick <jats:italic>Rhipicephalus microplus<\/jats:italic> is one of the most important ectoparasites with great sanitary and economic impact for cattle rearing worldwide. Ivermectin is commonly used to control tick populations, but its use over the last 30 years has led to the development of resistant populations of <jats:italic>R<\/jats:italic>. <jats:italic>microplus<\/jats:italic>, and a concomitant loss of efficacy. In this context, we aimed to determine the metabolic mechanisms that contribute to ivermectin resistance in a resistant strain of this species. We performed lethal time bioassays with inhibitors of detoxifying enzymes and xenobiotic transporters (four detoxification pathways) using two strains of ticks: a susceptible strain, Mozo, and a resistant strain, Juarez. We used four inhibitors to test the involvement of different families of proteins responsible for detoxification of ivermectin, namely cytochrome P450, esterases, glutathione-S-transferase, and <jats:underline>A<\/jats:underline>TP <jats:underline>B<\/jats:underline>inding <jats:underline>C<\/jats:underline>assette Transporters. We calculated the synergistic factor for each inhibitor and strain. To different degrees, all tested inhibitors altered the mortality rates in the strain Juarez, indicating that multiple mechanisms are responsible for the resistant phenotype. Detoxification mechanisms mediated by ABC transporters were observed to be the most important. Esterases, glutathione-S-transferases, and cytochrome-oxidases played less important roles in detoxification.<\/jats:p>","DOI":"10.1038\/s41598-018-30907-7","type":"journal-article","created":{"date-parts":[[2018,8,13]],"date-time":"2018-08-13T14:15:27Z","timestamp":1534169727000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Detoxification mechanisms involved in ivermectin resistance in the cattle tick, Rhipicephalus (Boophilus) microplus"],"prefix":"10.1038","volume":"8","author":[{"given":"Valeria Lis","family":"Le Gall","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme Marcondes","family":"Klafke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana Teixeira","family":"Torres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,8,17]]},"reference":[{"key":"30907_CR1","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.ympev.2014.03.017","volume":"76","author":"TD Burger","year":"2014","unstructured":"Burger, T. D., Shao, R. & Barker, S. C. Phylogenetic analysis of mitochondrial genome sequences indicates that the cattle tick, Rhipicephalus (Boophilus) microplus, contains a cryptic species. Mol. Phylogenet. Evol. 76, 241\u2013253 (2014).","journal-title":"Mol. Phylogenet. Evol."},{"key":"30907_CR2","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1590\/S1984-29612014042","volume":"23","author":"L Grisi","year":"2014","unstructured":"Grisi, L. et al. Reassessment of the potential economic impact of cattle parasites in Brazil. Rev. Bras. Parasitol. Vet. 23, 150\u2013156 (2014).","journal-title":"Rev. Bras. Parasitol. Vet."},{"key":"30907_CR3","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1590\/S0074-02761992000700003","volume":"87","author":"S Montenegro-James","year":"1992","unstructured":"Montenegro-James, S. Prevalence and control of babesiosis in the Americas. Mem Inst Oswaldo Cruz. 87, 27\u201336 (1992).","journal-title":"Mem Inst Oswaldo Cruz."},{"key":"30907_CR4","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.prevetmed.2013.10.006","volume":"113","author":"J Reck","year":"2014","unstructured":"Reck, J. et al. Does Rhipicephalus microplus tick infestation increase the risk for myiasis caused by Cochliomyia hominivorax in cattle? Prev Vet Med. 113, 59\u201362 (2014).","journal-title":"Prev Vet Med."},{"key":"30907_CR5","first-page":"64","volume":"149","author":"JR Martins","year":"2001","unstructured":"Martins, J. R. & Furlong, J. Avermectin resistance of the cattle tick Boophilus microplus in Brazil. Vet Rec. 149, 64 (2001).","journal-title":"Vet Rec."},{"key":"30907_CR6","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1016\/j.vetpar.2006.07.001","volume":"142","author":"GM Klafke","year":"2006","unstructured":"Klafke, G. M. et al. Larval Immersion Tests with ivermectin in populations of the cattle tick Rhipicephalus (Boophilus) microplus (Acari: Ixodidae) from State of S\u00e3o Paulo, Brazil. Vet. Parasitol. 142, 386\u2013390 (2006).","journal-title":"Vet. Parasitol."},{"key":"30907_CR7","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.vetpar.2009.10.003","volume":"168","author":"GM Klafke","year":"2010","unstructured":"Klafke, G. M., Albuquerque, T. A., Miller, R. J. & Schumaker, T. T. Selection of an ivermectin-resistant strain of Rhipicephalus microplus (Acari: Ixodidae) in Brazil. Vet. Parasitol. 168, 97\u2013104 (2010).","journal-title":"Vet. Parasitol."},{"key":"30907_CR8","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.vetpar.2011.09.018","volume":"184","author":"GM Klafke","year":"2012","unstructured":"Klafke, G. M., Castro-Janer, E., Mendes, M. C., Namindome, A. & Schumaker, T. T. S. Applicability of in vitro bioassays for the diagnosis of ivermectin resistance in Rhipicephalus microplus (Acari: Ixodidae). Vet. Parasitol. 184, 212\u2013220 (2012).","journal-title":"Vet. Parasitol."},{"key":"30907_CR9","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1016\/j.ibmb.2004.03.018","volume":"34","author":"J Hemingway","year":"2004","unstructured":"Hemingway, J., Hawkes, N. J., Mc Carroll, L. & Ranson, H. The molecular basis of insecticide resistance in mosquitoes. Insect Biochem. Mol. Biol. 34, 653\u2013665 (2004).","journal-title":"Insect Biochem. Mol. Biol."},{"key":"30907_CR10","doi-asserted-by":"publisher","first-page":"2657","DOI":"10.2741\/3403","volume":"14","author":"R Rosario-Cruz","year":"2009","unstructured":"Rosario-Cruz, R. et al. Genetic basis and impact of tick acaricide resistance. Front. Biosci. 14, 2657\u20132665 (2009).","journal-title":"Front. Biosci."},{"key":"30907_CR11","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1016\/j.ijpara.2011.08.004","volume":"41","author":"PC Pohl","year":"2011","unstructured":"Pohl, P. C. et al. ABC transporter efflux pumps: A defense mechanism against ivermectin in Rhipicephalus (Boophilus) microplus. Int. J. Parasitol. 41, 1323\u20131333 (2011).","journal-title":"Int. J. Parasitol."},{"key":"30907_CR12","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.pestbp.2015.01.004","volume":"121","author":"R Feyereisen","year":"2015","unstructured":"Feyereisen, R., Dermauw, W. & Van Leeuwen, T. Genotype to phenotype, the molecular and physiological dimensions of resistance in arthropods. Pesticide Biochemistry and Physiology 121, 61\u201377 (2015).","journal-title":"Pesticide Biochemistry and Physiology"},{"key":"30907_CR13","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1093\/jmedent\/36.5.533","volume":"36","author":"RJ Miller","year":"1999","unstructured":"Miller, R. J., Davey, R. B. & George, J. E. Characterization of pyrethroid resistance and susceptibility to coumaphos in Mexican Boophilus microplus (Acari: Ixodidae). J. Med. Entomol. 36, 533\u2013538 (1999).","journal-title":"J. Med. Entomol."},{"key":"30907_CR14","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1371\/journal.pntd.0000354","volume":"3","author":"C Passay","year":"2009","unstructured":"Passay, C. et al. The Effect of Insecticide Synergists on the Response of Scabies Mites to Pyrethroid Acaricides. PLoS Negl Trop Dis. 3, 354\u2013362 (2009).","journal-title":"PLoS Negl Trop Dis."},{"key":"30907_CR15","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1016\/j.vetpar.2007.05.003","volume":"147","author":"C Chevillon","year":"2007","unstructured":"Chevillon, C. et al. Accumulation of acaricide resistance mechanisms in Rhipicephalus (Boophilus) microplus (Acari: Ixodidae) populations from New Caledonia Island. Vet. Parasitol. 147, 276\u201388 (2007).","journal-title":"Vet. Parasitol."},{"key":"30907_CR16","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1603\/0022-2585-41.2.193","volume":"41","author":"AY Li","year":"2004","unstructured":"Li, A. Y., Davey, R. B., Miller, R. J. & George, J. E. Detection and characterization of amitraz resistance in the southern cattle tick, Boophilus microplus (Acari: Ixodidae). J. Med. Entomol. 41, 193\u2013200 (2004).","journal-title":"J. Med. Entomol."},{"key":"30907_CR17","doi-asserted-by":"publisher","first-page":"2345","DOI":"10.1007\/s00436-012-3089-1","volume":"111","author":"PC Pohl","year":"2012","unstructured":"Pohl, P. C. et al. ABC transporters as a multidrug detoxification mechanism in Rhipicephalus (Boophilus) microplus. Parasitol. Res. 111, 2345\u20132351 (2012).","journal-title":"Parasitol. Res."},{"key":"30907_CR18","doi-asserted-by":"crossref","unstructured":"Labb\u00e9, P., Alout, H., Djogb\u00e9nou, L., Pasteur, N. & Weill, M. Evolution of Resistance to Insecticide in Disease Vectors. Genetics and Evolution of Infectious Disease. 363\u2013409 (2011)","DOI":"10.1016\/B978-0-12-384890-1.00014-5"},{"key":"30907_CR19","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.ttbdis.2016.09.019","volume":"8","author":"GM Klafke","year":"2017","unstructured":"Klafke, G. M. et al. Multiple resistance to acaricides in field populations of Rhipicephalus microplus from Rio Grande do Sul state. Southern Brazil. Ticks Tick Borne Dis. 8, 73\u201380 (2017).","journal-title":"Southern Brazil. Ticks Tick Borne Dis."},{"key":"30907_CR20","unstructured":"FAO - Food And Agriculture Organisation. Resistance management and integrated parasite control in ruminants: Guidelines. Roma: Food and Agriculture Organisation, Animal Production and Health Division. ftp:\/\/ftp.fao.org\/docrep\/fao\/010\/ag014e\/ag014e00.pdf."},{"key":"30907_CR21","unstructured":"LeOra Software. In: J.L. Robertson, H. K. Preisler & Russel, R. M.(Eds) Polo Plus Probit and Logit Analysis, User\u2019s Guide. (Berkeley, 2003)."},{"key":"30907_CR22","doi-asserted-by":"crossref","unstructured":"Robertson, J. L., Russell, R. M., Preisler, H. K. & Savin, N. E. Bioassays with Arthropods, 2nd ed. (CRC Press, 2007).","DOI":"10.1201\/9781420004045"},{"key":"30907_CR23","doi-asserted-by":"publisher","first-page":"E113","DOI":"10.1073\/pnas.1213214110","volume":"110","author":"W Dermauw","year":"2012","unstructured":"Dermauw, W. et al. A link between host plant adaptation and pesticide resistance in the polyphagous spider mite Tetranychus urticae. Proc Natl Acad Sci USA 110, E113\u2013E122 (2012).","journal-title":"Proc Natl Acad Sci USA"},{"key":"30907_CR24","unstructured":"Finney, D. J. Probit analysis. Cambridge: The University Press (1971)."},{"key":"30907_CR25","doi-asserted-by":"crossref","unstructured":"Wickham, H. ggplot2: elegant graphics for data analysis. (Springer New York, 2009).","DOI":"10.1007\/978-0-387-98141-3"},{"key":"30907_CR26","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-01961-4","volume":"7","author":"E Kaplanoglu","year":"2017","unstructured":"Kaplanoglu, E., Chapman, P., Scott, I. M. & Donly, C. Overexpression of a cytochrome P450 and a UDP-glycosyltransferase is associated with imidacloprid resistance in the Colorado potato beetle, Leptinotarsa decemlineata. Scientific Reports 7, 1762 (2017).","journal-title":"Scientific Reports"},{"key":"30907_CR27","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2000-1-6-reviews3003","volume":"1","author":"D Werck-Reichhart","year":"2001","unstructured":"Werck-Reichhart, D. & Feyereisen, R. Cytochromes P450: a success story. Genome Biol. 1, REVIEWS3003, https:\/\/doi.org\/10.1186\/gb-2000-1-6-reviews3003 (2001).","journal-title":"Genome Biol."},{"issue":"4","key":"30907_CR28","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1603\/0022-0493-93.4.1269","volume":"93","author":"N Liu","year":"2000","unstructured":"Liu, N. & Yue, X. Insecticide resistance and cross-resistance in the house fly (Diptera: Muscidae). J Econ Entomol. 93(4), 1269\u201375 (2000).","journal-title":"J Econ Entomol."},{"key":"30907_CR29","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1002\/(SICI)1520-6327(1998)37:1<47::AID-ARCH6>3.0.CO;2-S","volume":"37","author":"S Kasai","year":"1998","unstructured":"Kasai, S., Weerashinghe, I. S. & Shono, T. P450 monooxygenases are an important mechanism of permethrin resistance in Culex quinquefasciatus Say larvae. Arch. Insect Biochem. Physiol. 37, 47\u201356 (1998).","journal-title":"Arch. Insect Biochem. Physiol."},{"key":"30907_CR30","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1016\/j.ibmb.2010.06.001","volume":"40","author":"K Itokawa","year":"2010","unstructured":"Itokawa, K. et al. Genomic structures of Cyp9m10in pyrethroid resistant and susceptible strains of Culex quinquefasciatus. Insect Biochem. Mol. Biol. 40, 631\u201340 (2010).","journal-title":"Insect Biochem. Mol. Biol."},{"key":"30907_CR31","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1101\/gr.087916.108","volume":"19","author":"CS Wondji","year":"2009","unstructured":"Wondji, C. S. et al. Two duplicated P450 genes are associated with pyrethroid resistance in Anopheles funestus, a major malaria vector. Genome Res. 19, 452\u201359 (2009).","journal-title":"Genome Res."},{"key":"30907_CR32","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1073\/pnas.1216705110","volume":"110","author":"JM Riveron","year":"2013","unstructured":"Riveron, J. M. et al. Directionally selected cytochrome P450 alleles are driving the spread of pyrethroid resistance in the major malaria vector Anopheles funestus. Proc. Natl. Acad. Sci. USA 110, 252\u201357 (2013).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"5590","key":"30907_CR33","doi-asserted-by":"publisher","first-page":"2253","DOI":"10.1126\/science.1074170","volume":"297","author":"PJ Daborn","year":"2002","unstructured":"Daborn, P. J. et al. A Single P450 Allele Associated with Insecticide Resistance in Drosophila. Science 297(5590), 2253\u20132256 (2002).","journal-title":"Science"},{"key":"30907_CR34","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1016\/j.ibmb.2010.05.008","volume":"40","author":"T Van Leeuwen","year":"2010","unstructured":"Van Leeuwen, T., Vontas, T., Tsagkarakou, A., Dermauw, W. & Tirry, L. Acaricide resistance mechanisms in the two-spotted spider mite Tetranychus urticae and other important Acari: A review. Insect Biochem. Mol. Biol. 40, 563\u2013572 (2010).","journal-title":"Insect Biochem. Mol. Biol."},{"issue":"5","key":"30907_CR35","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1603\/0022-0493-94.5.1209","volume":"94","author":"H Sanchez-Arroyo","year":"2001","unstructured":"Sanchez-Arroyo, H., Koehler, P. G. & Valles, S. M. Effects of the Synergists Piperonyl Butoxide and S,S,S-Tributyl Phosphorotrithioate on Propoxur Pharmacokinetics in Blattella germanica (Blattodea: Blattellidae). Journal of Economic Entomology. 94(5), 1209\u20131216 (2001).","journal-title":"Journal of Economic Entomology."},{"issue":"10","key":"30907_CR36","first-page":"981","volume":"10","author":"AS Dehkordi","year":"2017","unstructured":"Dehkordi, A. S. et al. Synergists action of piperonyl butoxide and S,S,S-tributyl phosphorotrithioate on toxicity of carbamate insecticides against Blattella germanica. Asian Pacific. Journal of Tropical Medicine. 10(10), 981\u2013986 (2017).","journal-title":"Journal of Tropical Medicine."},{"issue":"1","key":"30907_CR37","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1515\/jppr-2016-0010","volume":"56","author":"IS Abdallah","year":"2016","unstructured":"Abdallah, I. S., Abou-Yousef, H. M., Fouad, E. A. & El-Hady Kandil, M. A. The role of detoxifying enzymes in the resistance of the cowpea aphid (Aphis craccivora Koch) to thiamethoxam. Journal of Plant Protection Research. 56(1), 67\u201372 (2016).","journal-title":"Journal of Plant Protection Research."},{"key":"30907_CR38","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-017-1960-3","volume":"16","author":"SK Dadzie","year":"2017","unstructured":"Dadzie, S. K. et al. Evaluation of piperonyl butoxide in enhancing the efficacy of pyrethroid insecticides against resistant Anopheles gambiae s.l. in Ghana. Malaria Journal 16, 342 (2017).","journal-title":"Malaria Journal"},{"issue":"5","key":"30907_CR39","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1603\/0022-0493-94.5.1209","volume":"94","author":"H Sanchez-Arroyo","year":"2001","unstructured":"Sanchez-Arroyo, H., Koehler, P. G. & Valles, S. M. Effects of the synergists piperonyl butoxide and S, S, S-tributyl phosphorotrithioate on propoxur pharmacokinetics in Blatella germanica (Blattodea: Blattelidae). J Econ Entomol 94(5), 1209\u20131216 (2001).","journal-title":"J Econ Entomol"},{"key":"30907_CR40","doi-asserted-by":"crossref","unstructured":"M\u00fcller, P. et al. Field-caught permethrin-resistant Anopheles gambiae overexpress CYP6P3, a P450 that metabolises pyrethroids.PLoS Genet. 4(11), e1000286 (2008).","DOI":"10.1371\/journal.pgen.1000286"},{"issue":"1","key":"30907_CR41","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.pestbp.2006.06.002","volume":"87","author":"YC Zhu","year":"2007","unstructured":"Zhu, Y. C., Gordon, L. S. & Ming, S. C. Comparative study on glutathione S-transferase activity, cDNA, and gene expression between malathion susceptible and resistant strains of the tarnished plant bug, Lygus lineolaris. Pesticide Biochemistry and Physiology 87(1), 62\u201372 (2007).","journal-title":"Pesticide Biochemistry and Physiology"},{"key":"30907_CR42","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1590\/S0074-02762012000400001","volume":"107","author":"IR Montella","year":"2012","unstructured":"Montella, I. R., Schama, R. & Valle, D. The classification of esterases: an important gene family involved in insecticide resistance\u2013a review. Mem. Inst. Oswaldo Cruz. 107, 437\u2013449 (2012).","journal-title":"Mem. Inst. Oswaldo Cruz."},{"issue":"3","key":"30907_CR43","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/S0965-1748(97)00109-4","volume":"28","author":"PM Campbell","year":"1998","unstructured":"Campbell, P. M., Newcomb, R. D., Russell, R. J. & Oakeshott, J. G.Two different amino acid substitutions in the ali-esterase, E3, confer alternative types of organophosphorus insecticide resistance in the sheep blowfly, Lucilia cuprina. Insect Biochemistry and Molecular Biology 28(3), 139\u2013150 (1998).","journal-title":"Insect Biochemistry and Molecular Biology"},{"issue":"3-4","key":"30907_CR44","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1016\/j.vetpar.2006.04.010","volume":"140","author":"RA Carvalho","year":"2006","unstructured":"Carvalho, R. A., Torres, T. T. & de Azeredo-Espin, A. M. A survey of mutations in the Cochliomyia hominivorax (Diptera: Calliphoridae) esterase E3 gene associated with organophosphate resistance and the molecular identification of mutant alleles. Vet Parasitol 140(3-4), 344\u2013351 (2006).","journal-title":"Vet Parasitol"},{"key":"30907_CR45","doi-asserted-by":"crossref","unstructured":"Carvalho, R. A., Torres, T. T., Paniago, M. G. & Azeredo-Espin, A. M. Molecular characterization of esterase E3 gene associated with organophosphorus insecticide resistance in the New World screwworm fly, Cochliomyia hominivorax. Med Vet Entomol. Suppl (1), 86\u201391(2009).","DOI":"10.1111\/j.1365-2915.2008.00788.x"},{"key":"30907_CR46","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1006\/pest.1996.0044","volume":"55","author":"M Zhang","year":"1996","unstructured":"Zhang, M. & Scott, J. G. Cytochrome b5 is essential for cyto- chrome P450 6D1-mediated cypermethrin resistance in LPR house flies. Pestic Biochem Physiol 55, 150\u2013156 (1996).","journal-title":"Pestic Biochem Physiol"},{"key":"30907_CR47","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/S0923-2508(01)01193-7","volume":"152","author":"CF Higgins","year":"2001","unstructured":"Higgins, C. F. ABC transporters: physiology, structure and mechanism\u2013an overview. Res. Microbiol. 152, 205\u2013210 (2001).","journal-title":"Res. Microbiol."},{"key":"30907_CR48","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1016\/0005-2736(73)90191-0","volume":"323","author":"K Dano","year":"1973","unstructured":"Dano, K. Active outward transport of daunomycin in resistant Ehrlich ascites tumor cells. Biochim. Biophys. Acta. 323, 466\u2013483 (1973).","journal-title":"Biochim. Biophys. Acta."},{"key":"30907_CR49","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1038\/316820a0","volume":"316","author":"N Kartner","year":"1985","unstructured":"Kartner, N., Everndenporelle, D., Bradley, G. & Ling, V. Detection of P-glycoprotein in multidrug-resistant cell-lines by monoclonal-antibodies. Nature 316, 820\u2013823 (1985).","journal-title":"Nature"},{"key":"30907_CR50","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1046\/j.1365-2915.2002.00365.x","volume":"16","author":"DS Buss","year":"2002","unstructured":"Buss, D. S., McCaffery, A. R. & Callaghan, A. Evidence for P-glycoprotein modification of insecticide toxicity in mosquitoes of the Culex pipiens complex. Med. Vet. Entomol. 16, 218\u2013222 (2002).","journal-title":"Med. Vet. Entomol."},{"key":"30907_CR51","doi-asserted-by":"publisher","first-page":"e36366","DOI":"10.1371\/journal.pone.0036366","volume":"7","author":"AX Silva","year":"2012","unstructured":"Silva, A. X., Jander, G., Samaniego, H., Ramsey, J. S. & Figueroa, C. C. Insecticide resistance mechanisms in the green peach aphid Myzus persicae (Hemiptera: Aphididae) I: a transcriptomic survey. PLoS ONE, 7, e36366 (2012).","journal-title":"PLoS ONE,"},{"key":"30907_CR52","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1016\/j.ibmb.2013.04.006","volume":"43","author":"L Luo","year":"2013","unstructured":"Luo, L., Sun, Y. J. & Wu, Y. J. Abamectin resistance in Drosophila is related to increased expression of P-glycoprotein via the dEGFR and dAkt pathways. Insect Biochem. Mol. Biol. 43, 627\u2013634 (2013).","journal-title":"Insect Biochem. Mol. Biol."},{"key":"30907_CR53","doi-asserted-by":"publisher","first-page":"e26796","DOI":"10.1371\/journal.pone.0026796","volume":"6","author":"DJ Hawthorne","year":"2011","unstructured":"Hawthorne, D. J. & Dively, G. P. Killing them with kindness? In-hive medications may inhibit xenobiotic efflux transporters and endanger honey bees. PLoS ONE, 6, e26796 (2011).","journal-title":"PLoS ONE,"},{"issue":"1","key":"30907_CR54","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1111\/mve.12093","volume":"29","author":"C Cafarchia","year":"2015","unstructured":"Cafarchia, C. et al. Potential role of ATP-binding cassette transporters against acaricides in the brown dog tick Rhipicephalus sanguineus sensu lato. Med Vet Entomol. 29(1), 88\u201393 (2015).","journal-title":"Med Vet Entomol."},{"key":"30907_CR55","doi-asserted-by":"publisher","first-page":"443e450","DOI":"10.1016\/S0305-0491(98)10137-2","volume":"121","author":"L Podsiadlowski","year":"1998","unstructured":"Podsiadlowski, L., Matha, V. & Vilcinskas, A. Detection of a P-glycoprotein related pump in Chironomus larvae and its inhibition by verapamil and cyclosporin A. Comp. Biochem. Physiol. B Biochem. Mol. Biol. 121, 443e450 (1998).","journal-title":"Comp. Biochem. Physiol. B Biochem. Mol. Biol."},{"issue":"4","key":"30907_CR56","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1603\/EC11082","volume":"104","author":"F Couso-Ferrer","year":"2011","unstructured":"Couso-Ferrer, F. et al. Cross-resistance to insecticides in a malathion-resistant strain of Ceratitis capitata (Diptera: Tephritidae). J Econ Entomol. 104(4), 1349\u201356 (2011).","journal-title":"J Econ Entomol."},{"key":"30907_CR57","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.ibmb.2013.11.001","volume":"45","author":"W Dermauw","year":"2014","unstructured":"Dermauw, W. & Van Leeuwen, T. The ABC gene family in arthropods: Comparative genomics and role in insecticide transport and resistance. Insect Biochemistry and Molecular Biology 45, 89\u2013110 (2014).","journal-title":"Insect Biochemistry and Molecular Biology"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-30907-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-30907-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-30907-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T08:38:17Z","timestamp":1671611897000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-30907-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,17]]},"references-count":57,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["30907"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-30907-7","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,17]]},"assertion":[{"value":"26 March 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 July 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 August 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"12401"}}