Ecologically Appropriate Xenobiotics Induce Cytochrome P450s in Apis mellifera

Abstract

BackgroundHoney bees are exposed to phytochemicals through the nectar, pollen and propolis consumed to sustain the colony. They may also encounter mycotoxins produced by Aspergillus fungi infesting pollen in beebread. Moreover, bees are exposed to agricultural pesticides, particularly in-hive acaricides used against the parasite Varroa destructor. They cope with these and other xenobiotics primarily through enzymatic detoxificative processes, but the regulation of detoxificative enzymes in honey bees remains largely unexplored.Methodology/Principal FindingsWe used several approaches to ascertain effects of dietary toxins on bee susceptibility to synthetic and natural xenobiotics, including the acaricide tau-fluvalinate, the agricultural pesticide imidacloprid, and the naturally occurring mycotoxin aflatoxin. We administered potential inducers of cytochrome P450 enzymes, the principal biochemical system for Phase 1 detoxification in insects, to investigate how detoxification is regulated. The drug phenobarbital induces P450s in many insects, yet feeding bees with phenobarbital had no effect on the toxicity of tau-fluvalinate, a pesticide known to be detoxified by bee P450s. Similarly, no P450 induction, as measured by tau-fluvalinate tolerance, occurred in bees fed xanthotoxin, salicylic acid, or indole-3-carbinol, all of which induce P450s in other insects. Only quercetin, a common pollen and honey constituent, reduced tau-fluvalinate toxicity. In microarray comparisons no change in detoxificative gene expression was detected in phenobarbital-treated bees. However, northern blot analyses of guts of bees fed extracts of honey, pollen and propolis showed elevated expression of three CYP6AS P450 genes. Diet did not influence tau-fluvalinate or imidacloprid toxicity in bioassays; however, aflatoxin toxicity was higher in bees consuming sucrose or high-fructose corn syrup than in bees consuming honey.Conclusions/SignificanceThese results suggest that regulation of honey bee P450s is tuned to chemicals occurring naturally in the hive environment and that, in terms of toxicological capacity, a diet of sugar is not equivalent to a diet of honey.

Honey constituents up-regulate detoxification and immunity genes in the western honey bee Apis mellifera

“…Honey extracts have previously been documented to up-regulate transcription of genes in the CYP6AS (18) and CYP9Q (16) subfamilies. We have now identified the specific constituents responsible for induction of these genes.…”

Transcriptional signatures of parasitization and markers of colony decline in Varroa-infested honey bees (Apis mellifera)

“…: 314A1, GB45725; 6AS10, GB48738; 6AS10, GB40285). P450s play multiple metabolic roles and are important for their detoxification activity against natural and synthetic toxins (Feyereisen, 2005;Johnson et al, 2012). In general, due to their role in detoxification, P450s genes appear to be up-regulated upon exposure to abiotic stressors such as insecticides and acaricides (Feyereisen, 2005;Li et al, 2007).…”

Pharmacophagy and pharmacophory: mechanisms of self-medication and disease prevention in the honeybee colony (Apis mellifera)

“…Healthy worker bees treated with such extracts (ethanol and methanol) reduce their individual innate immunity and upregulate detoxification genes (Johnson et al 2012;Simone et al 2009). In addition, much lower microbe levels were detected in healthy colonies treated with different ethanolic propolis extracts (Simone et al 2009).…”

“…Nutrigenomic studies used methanol and ethylacetate extracts of honey to measure transcriptional changes in healthy bees (Johnson et al 2012;Mao et al 2011Mao et al , 2013. As a common result, genes related to detoxification processes and innate immunity (antimicrobial peptide genes) were upregulated in groups of bees fed with these extracts.…”