Portal de Periódicos da CAPES

Unravelling the Molecular Determinants of Bee Sensitivity to Neonicotinoid Insecticides

2018; Elsevier BV; Volume: 28; Issue: 7 Linguagem: Inglês

10.1016/j.cub.2018.02.045

1879-0445

Cristina Manjón, Bartlomiej J. Troczka, Marion Zaworra, Katherine Beadle, Emma Randall, Gillian Hertlein, Kumar Saurabh Singh, Christoph T. Zimmer, Rafael A. Homem, Bettina Lueke, Rebecca J. Reid, Laura Kor, Maxie Kohler, Jürgen Benting, Martin S. Williamson, T. G. E. Davies, L. M. Field, Chris Bass, Ralf Nauen,

Insect-Plant Interactions and Control

The impact of neonicotinoid insecticides on the health of bee pollinators is a topic of intensive research and considerable current debate [1Cressey D. The bitter battle over the world's most popular insecticides.Nature. 2017; 551: 156-158Crossref PubMed Scopus (43) Google Scholar]. As insecticides, certain neonicotinoids, i.e., N-nitroguanidine compounds such as imidacloprid and thiamethoxam, are as intrinsically toxic to bees as to the insect pests they target. However, this is not the case for all neonicotinoids, with honeybees orders of magnitude less sensitive to N-cyanoamidine compounds such as thiacloprid [2Iwasa T. Motoyama N. Ambrose J.T. Roe M. Mechanism for the differential toxicity of neonicotinoid insecticides in the honey bee, Apis mellifera.Crop Prot. 2004; 23: 371-378Crossref Scopus (544) Google Scholar]. Although previous work has suggested that this is due to rapid metabolism of these compounds [2Iwasa T. Motoyama N. Ambrose J.T. Roe M. Mechanism for the differential toxicity of neonicotinoid insecticides in the honey bee, Apis mellifera.Crop Prot. 2004; 23: 371-378Crossref Scopus (544) Google Scholar, 3Alptekin S. Bass C. Nicholls C. Paine M.J. Clark S.J. Field L. Moores G.D. Induced thiacloprid insensitivity in honeybees (Apis mellifera L.) is associated with up-regulation of detoxification genes.Insect Mol. Biol. 2016; 25: 171-180Crossref PubMed Scopus (37) Google Scholar, 4Brunet J.L. Badiou A. Belzunces L.P. In vivo metabolic fate of [14C]-acetamiprid in six biological compartments of the honeybee, Apis mellifera L.Pest Manag. Sci. 2005; 61: 742-748Crossref PubMed Scopus (78) Google Scholar, 5Suchail S. De Sousa G. Rahmani R. Belzunces L.P. In vivo distribution and metabolisation of 14C-imidacloprid in different compartments of Apis mellifera L.Pest Manag. Sci. 2004; 60: 1056-1062Crossref PubMed Scopus (110) Google Scholar], the specific gene(s) or enzyme(s) involved remain unknown. Here, we show that the sensitivity of the two most economically important bee species to neonicotinoids is determined by cytochrome P450s of the CYP9Q subfamily. Radioligand binding and inhibitor assays showed that variation in honeybee sensitivity to N-nitroguanidine and N-cyanoamidine neonicotinoids does not reside in differences in their affinity for the receptor but rather in divergent metabolism by P450s. Functional expression of the entire CYP3 clade of P450s from honeybees identified a single P450, CYP9Q3, that metabolizes thiacloprid with high efficiency but has little activity against imidacloprid. We demonstrate that bumble bees also exhibit profound differences in their sensitivity to different neonicotinoids, and we identify CYP9Q4 as a functional ortholog of honeybee CYP9Q3 and a key metabolic determinant of neonicotinoid sensitivity in this species. Our results demonstrate that bee pollinators are equipped with biochemical defense systems that define their sensitivity to insecticides and this knowledge can be leveraged to safeguard bee health.