title: Synergistic and compensatory effects of two point mutations conferring target-site resistance to fipronil in the insect GABA receptor RDL.
abstract: Insecticide resistance can arise from a variety of mechanisms, including changes to the target site, but is often associated with substantial fitness costs to insects. Here we describe two resistance-associated target-site mutations that have synergistic and compensatory effects that combine to produce high and persistent levels of resistance to fipronil, an insecticide targeting on γ-aminobytyric acid (GABA) receptors. In Nilaparvata lugens, a major pest of rice crops in many parts of Asia, we have identified a single point mutation (A302S) in the GABA receptor RDL that has been identified previously in other species and which confers low levels of resistance to fipronil (23-fold) in N. lugans. In addition, we have identified a second resistance-associated RDL mutation (R300Q) that, in combination with A302S, is associated with much higher levels of resistance (237-fold). The R300Q mutation has not been detected in the absence of A302S in either laboratory-selected or field populations, presumably due to the high fitness cost associated with this mutation. Significantly, it appears that the A302S mutation is able to compensate for deleterious effects of R300Q mutation on fitness cost. These findings identify a novel resistance mechanism and may have important implications for the spread of insecticide resistance.
authors.affiliation: Key Laboratory of Integrated Management of Crop Diseases and Pests (Ministry of Education), College of Plant Protection, Nanjing Agricultural University, Weigang 1, Nanjing 210095, China.
authors.forename: Yixi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Integrated Management of Crop Diseases and Pests (Ministry of Education), College of Plant Protection, Nanjing Agricultural University, Weigang 1, Nanjing 210095, China.
authors.forename: Xiangkun
authors.initials: X
authors.lastname: Meng
authors.affiliation: Key Laboratory of Integrated Management of Crop Diseases and Pests (Ministry of Education), College of Plant Protection, Nanjing Agricultural University, Weigang 1, Nanjing 210095, China.
authors.forename: Yuanxue
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Key Laboratory of Integrated Management of Crop Diseases and Pests (Ministry of Education), College of Plant Protection, Nanjing Agricultural University, Weigang 1, Nanjing 210095, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Key Laboratory of Integrated Management of Crop Diseases and Pests (Ministry of Education), College of Plant Protection, Nanjing Agricultural University, Weigang 1, Nanjing 210095, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Rice Technology Research and Development Center, China National Rice Research Institute, Hangzhou 310006, China.
authors.forename: Baojun
authors.initials: B
authors.lastname: Yang
authors.affiliation: Key Laboratory of Integrated Management of Crop Diseases and Pests (Ministry of Education), College of Plant Protection, Nanjing Agricultural University, Weigang 1, Nanjing 210095, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Integrated Management of Crop Diseases and Pests (Ministry of Education), College of Plant Protection, Nanjing Agricultural University, Weigang 1, Nanjing 210095, China.
authors.forename: Chunrui
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Neuroscience, Physiology &Pharmacology, University College London, London, WC1E 6BT, UK.
authors.forename: Neil S
authors.initials: NS
authors.lastname: Millar
authors.affiliation: Key Laboratory of Integrated Management of Crop Diseases and Pests (Ministry of Education), College of Plant Protection, Nanjing Agricultural University, Weigang 1, Nanjing 210095, China.
authors.forename: Zewen
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D055724:Electrophysiological Phenomena / Q000235:genetics; D006430:Hemiptera / Q000235:genetics*; D019476:Insect Proteins / Q000235:genetics*; D007305:Insecticide Resistance / Q000235:genetics*; D007306:Insecticides / Q000494:pharmacology; D009865:Oocytes / Q000378:metabolism / Q000502:physiology; D017354:Point Mutation; D011720:Pyrazoles / Q000494:pharmacology*; D018079:Receptors, GABA / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D013489:Suppression, Genetic; D014981:Xenopus
chemical_list: D019476:Insect Proteins; D007306:Insecticides; D011720:Pyrazoles; D018079:Receptors, GABA; C082360:fipronil