Partitioning the roles of CYP6G1 and gut microbes in the metabolism of the insecticide imidacloprid in Drosophila melanogaster

Fusetto, Roberto; Denecke, Shane; Perry, Trent; O’Hair, Richard A. J.; Batterham, Philip

doi:10.1038/s41598-017-09800-2

Cited by 44 publications

(35 citation statements)

References 62 publications

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“…Cyp6g2 (DS = 1) may be involved in juvenile hormone metabolism (Christesen et al, 2016), but also has the capacity to detoxify multiple classes of insecticides if expressed ectopically (Daborn et al, 2007; Denecke et al, 2017). Cyp6g2 is a paralog of Cyp6g1 (DS = 4), which encodes a detoxification enzyme with very broad substrate specificity (Battlay et al, 2018; 2016; Daborn et al, 2002; 2007; Fusetto et al, 2017; Joußen et al, 2008; J. Schmidt et al, 2010), and so Cyp6g2 may have a pre-adapted detoxification capacity.…”

Section: Discussionmentioning

confidence: 99%

Identifying candidate detoxification genes in the ecdysteroid kinase-like (EcKL) and cytochrome P450 gene families inDrosophila melanogasterby integrating evolutionary and transcriptomic data

Scanlan

Battlay

et al. 2020

Preprint

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1 and cytochrome P450 gene families in Drosophila melanogaster by integrating 2 evolutionary and transcriptomic data 3 4Abstract: The capacity to detoxify toxic compounds is essential for adaptation to the 22 ecological niches of many organisms, especially insects. However, detoxification in 23 insects is often viewed through the lens of mammalian detoxification research, even 24 though the organ and enzyme systems involved have diverged for over half a billion 25 years. Phosphorylation is a non-canonical phase II detoxification reaction that, 26 among animals, occurs near exclusively in insects, but the enzymes responsible 27 have never been cloned or otherwise identified. We propose the hypothesis that 28 members of the arthropod-specific ecdysteroid kinase-like (EcKL) gene family 29 encode detoxicative kinases. To test this hypothesis, we annotated the EcKL gene 30 family in 12 species of Drosophila and explored their evolution within the genus. 31 Many ancestral EcKL clades are evolutionarily unstable and have experienced 32 repeated gene gain and loss events, while others are conserved as single copy 33 orthologs. Leveraging multiple published gene expression datasets from D. 34 melanogaster, and using the cytochrome P450s-a canonical detoxification family-35 as a test case, we demonstrate relationships between xenobiotic induction, 36 detoxification tissue-enriched expression and evolutionary instability in the EcKLs 37 and the P450s. We also found previously unreported genomic and transcriptomic 38 variation in a number of EcKLs and P450s associated with toxic stress phenotypes 39 using a targeted phenome-wide association study (PheWAS) approach. Lastly, we 40 devised a systematic method for identifying candidate detoxification genes in large 41 gene families that is concordant with experimentally determined functions of P450 42 genes in D. melanogaster. Applying this method to the EcKLs suggested a 43 significant proportion of these genes play roles in detoxification, and that the EcKLs 44 may constitute a detoxification gene family in insects. Additionally, we estimate that 45 between 11-16 uncharacterised D. melanogaster P450s are strong detoxification 46 candidates. 47 48 Highlights 49 50• The poorly characterised ecdysteroid kinase-like (EcKL) gene family is 51 hypothesised to encode enzymes responsible for detoxification by 52 phosphorylation in insects. 53• An integrative 'detoxification score' method accurately categorises the known 54 functions of a canonical detoxification family, the cytochrome P450s, and 55 suggests many EcKLs are also involved in detoxification. 56• A targeted phenome-wide association study finds novel associations between 57 EcKL/P450 variation and a number of toxic stress phenotypes, such as two 58 unlinked EcKL paralogs that are both associated with developmental 59 methylmercury resistance. 60 61 1983 131 132The identification of detoxification genes and enzymes is an important part of 133 bridging the gap between toxicology, chemical ecology and functional genomics in ...

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Section: Discussionmentioning

confidence: 99%

Identifying candidate detoxification genes in the ecdysteroid kinase-like (EcKL) and cytochrome P450 gene families inDrosophila melanogasterby integrating evolutionary and transcriptomic data

Scanlan

Battlay

et al. 2020

Preprint

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“…Of the entire P450 enzyme lineage, this clade has been particularly strongly linked to xenobiotic detoxification in insects (Li, Schuler, & Berenbaum, ). The CYP6 group has been found to contribute to neonicotinoid (imidacloprid) metabolism and resistance in flies in multiple studies (Daborn, Boundy, Yen, & Pittendrigh, ; Fusetto, Denecke, Perry, Richard, & Batterham, ; Sparks et al, ). The roles of two members of the related CYP9 group (CYP9Q4 and CYP9Q6) in neonicotinoid metabolism have been functionally validated in bumble bees (Manjon et al, ; Troczka et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…Of the entire P450 enzyme lineage, this clade has been particularly strongly linked to xenobiotic detoxification in insects (Li, Schuler, & Berenbaum, 2007). The CYP6 group has been found to contribute to neonicotinoid (imidacloprid) metabolism and resistance in flies in multiple studies (Daborn, Boundy, Yen, & Pittendrigh, 2001;Fusetto, Denecke, Perry, Richard, & Batterham, 2017;Sparks et al, 2012).…”

Section: Diet Impacts the Expression Of Detoxificationrelated Genesmentioning

confidence: 99%

Transcriptome analysis reveals nutrition‐ and age‐related patterns of gene expression in the fat body of pre‐overwintering bumble bee queens

et al. 2020

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Many diapausing insects undergo a nutrient storage period prior to their entry into diapause. Bumble bee queens diapause as adults in the winter preceding their spring nest initiation period. Before diapause, they sequester glycogen and lipids, which they metabolize during the overwintering period. We used RNA sequencing to examine how age and nectar diet (specifically, the concentration of sucrose in nectar) impact gene expression in the pre‐overwintering bumble bee queen fat body, the “liver‐like” organ in insects with broad functions related to nutrient storage and metabolism. We found that diet on its own, and in combination with age, impacts the expression of genes involved in detoxification. Age was also a strong driver of gene expression, especially at earlier ages (up to 3 days). In addition to these molecular correlates of diet and age, we also found a putative molecular signature of diapause entry or preparation in adult queens in the oldest age group (12 days) fed the most sucrose‐rich diet, based on comparisons between our data set and another transcriptome data set from bumble bee queens. This transcriptomic pattern suggests that preparation for (or entry into) diapause might be in part mediated by nutritional state in bumble bee queens. Collectively, these findings show that there are molecular processes in the fat body that are responsive to sucrose levels in the diet and/or associated with age‐related maturational changes. A better understanding of these processes may shed light on important aspects of bumble bee biology, such as queen responses to nutritional and other forms of stress, and the factors that regulate their entrance into diapause.

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“…Human CYP3A4 and fruit fly CYP6G1 were proved to hydroxylate imidacloprid to its 5-hydroxy metabolite (Fusetto et al 2017). Therefore, cytochrome P450 monooxygenases were searched in the annotated proteins of H. latericoloratus CGMCC 16346 and P. indica CGMCC 6648.…”

Section: Analysis Of Cytochrome P450 Monooxygenase Genes and Inhibitimentioning

confidence: 99%

“…Neighbor-joining phylogenetic tree based on bacterial CYP450, human CYP3A4 and fruit fly CYP6G1 sequences. Human CYP3A4 and fruit fly CYP6G1 were reported to degrade imidacloprid via the hydroxylation pathway (Fusetto et al 2017) Although imidacloprid was detected in surface water at level of micrograms per liter, it acts as an insect neurotoxin and is toxic even at low concentrations. Van Dijk et al (2013) proved that imidacloprid concentrations as low as 0.01 ppb led to significant reduction in the number of macroinvertebrates in surface waters.…”

Section: Figmentioning

confidence: 99%

Oligotrophic bacterium Hymenobacter latericoloratus CGMCC 16346 degrades the neonicotinoid imidacloprid in surface water

et al. 2020

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The intensive and extensive application of imidacloprid in agriculture has resulted in water pollution and risks to aquatic invertebrates. However, pure bacteria remediation of imidacloprid in surface water environments has not been studied. Here, we isolated an imidacloprid-degrading bacterium from a water environment, examined its imidacloprid degradation in pure culture and surface water, sequenced its genome, and compared its Clusters of Orthologous Groups (COG) protein categorization with that for another imidacloprid-degrading bacterium. The isolate was an obligate oligotrophic bacterium, Hymenobacter latericoloratus CGMCC 16346, which degraded imidacloprid via hydroxylation by co-metabolism in pure culture. Resting cells degraded 64.4% of 100 mg/L imidacloprid in 6 days in the presence of co-substrate maltose, and growing culture degraded 40.8% of imidacloprid in 10 days. H. latericoloratus CGMCC 16346 degraded imidacloprid in surface water without co-substrate supplementation and retained imidacloprid-degrading activity after 30 days. The half-life of imidacloprid in surface water was decreased from 173.3 days in the control to 57.8 days by CGMCC 16346 inoculation. Genome sequencing and COG analysis indicated that carbohydrate metabolism and transport, cell wall/membrane biogenesis, and defense mechanisms are enriched in H. latericoloratus CGMCC 16346 compared with the copiotrophic imidacloprid-degrading Pseudoxanthomonas indica CGMCC 6648, indicating that H. latericoloratus CGMCC 16346 is adapted to live in oligotrophic water environments and biofilms. H. latericoloratus CGMCC 16346 is a promising bioremediation agent for elimination of imidacloprid contamination from surface water.

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Partitioning the roles of CYP6G1 and gut microbes in the metabolism of the insecticide imidacloprid in Drosophila melanogaster

Cited by 44 publications

References 62 publications

Identifying candidate detoxification genes in the ecdysteroid kinase-like (EcKL) and cytochrome P450 gene families inDrosophila melanogasterby integrating evolutionary and transcriptomic data

Identifying candidate detoxification genes in the ecdysteroid kinase-like (EcKL) and cytochrome P450 gene families inDrosophila melanogasterby integrating evolutionary and transcriptomic data

Transcriptome analysis reveals nutrition‐ and age‐related patterns of gene expression in the fat body of pre‐overwintering bumble bee queens

Oligotrophic bacterium Hymenobacter latericoloratus CGMCC 16346 degrades the neonicotinoid imidacloprid in surface water

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