title: MAPK signaling pathway alters expression of midgut ALP and ABCC genes and causes resistance to Bacillus thuringiensis Cry1Ac toxin in diamondback moth.
abstract: Insecticidal crystal toxins derived from the soil bacterium Bacillus thuringiensis (Bt) are widely used as biopesticide sprays or expressed in transgenic crops to control insect pests. However, large-scale use of Bt has led to field-evolved resistance in several lepidopteran pests. Resistance to Bt Cry1Ac toxin in the diamondback moth, Plutella xylostella (L.), was previously mapped to a multigenic resistance locus (BtR-1). Here, we assembled the 3.15 Mb BtR-1 locus and found high-level resistance to Cry1Ac and Bt biopesticide in four independent P. xylostella strains were all associated with differential expression of a midgut membrane-bound alkaline phosphatase (ALP) outside this locus and a suite of ATP-binding cassette transporter subfamily C (ABCC) genes inside this locus. The interplay between these resistance genes is controlled by a previously uncharacterized trans-regulatory mechanism via the mitogen-activated protein kinase (MAPK) signaling pathway. Molecular, biochemical, and functional analyses have established ALP as a functional Cry1Ac receptor. Phenotypic association experiments revealed that the recessive Cry1Ac resistance was tightly linked to down-regulation of ALP, ABCC2 and ABCC3, whereas it was not linked to up-regulation of ABCC1. Silencing of ABCC2 and ABCC3 in susceptible larvae reduced their susceptibility to Cry1Ac but did not affect the expression of ALP, whereas suppression of MAP4K4, a constitutively transcriptionally-activated MAPK upstream gene within the BtR-1 locus, led to a transient recovery of gene expression thereby restoring the susceptibility in resistant larvae. These results highlight a crucial role for ALP and ABCC genes in field-evolved resistance to Cry1Ac and reveal a novel trans-regulatory signaling mechanism responsible for modulating the expression of these pivotal genes in P. xylostella.
authors: Department of Plant Protection, Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing, China.
authors: Zhaojiang
authors: Z
authors: Guo
authors: Department of Plant Protection, Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing, China.
authors: Shi
authors: S
authors: Kang
authors: Department of Plant Protection, Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing, China.
authors: Defeng
authors: D
authors: Chen
authors: Department of Plant Protection, Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing, China.
authors: Qingjun
authors: Q
authors: Wu
authors: Department of Plant Protection, Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing, China.
authors: Shaoli
authors: S
authors: Wang
authors: Department of Plant Protection, Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing, China.
authors: Wen
authors: W
authors: Xie
authors: Department of Plant Protection, Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing, China.
authors: Xun
authors: X
authors: Zhu
authors: School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Australia.
authors: Simon W
authors: SW
authors: Baxter
authors: Department of Entomology, University of Kentucky, Lexington, Kentucky, United States of America.
authors: Xuguo
authors: X
authors: Zhou
authors: Department of Entomology and Plant Pathology, University of Tennessee, Knoxville, Tennessee, United States of America.
authors: Juan Luis
authors: JL
authors: Jurat-Fuentes
authors: Department of Plant Protection, Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing, China.
authors: Youjun
authors: Y
authors: Zhang
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001407:Bacillus / Q000378:metabolism; D000083722:Bacillus thuringiensis Toxins; D001426:Bacterial Proteins / Q000494:pharmacology* / Q000633:toxicity; D061046:Biological Control Agents / Q000494:pharmacology* / Q000633:toxicity; D004731:Endotoxins / Q000494:pharmacology* / Q000633:toxicity; D006460:Hemolysin Proteins / Q000494:pharmacology* / Q000633:toxicity; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D007305:Insecticide Resistance; D007413:Intestinal Mucosa / Q000378:metabolism; D020935:MAP Kinase Signaling System; D009036:Moths / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding
chemical_list: D018528:ATP-Binding Cassette Transporters; D000083722:Bacillus thuringiensis Toxins; D001426:Bacterial Proteins; D061046:Biological Control Agents; D004731:Endotoxins; D006460:Hemolysin Proteins; D019476:Insect Proteins; C030956:insecticidal crystal protein, Bacillus Thuringiensis; D000469:Alkaline Phosphatase