Disruption of quercetin metabolism by fungicide affects energy production in honey bees (Apis mellifera)

Abstract

Cytochrome P450 monooxygenases (P450) in the honey bee, , detoxify phytochemicals in honey and pollen. The flavonol quercetin is found ubiquitously and abundantly in pollen and frequently at lower concentrations in honey. Worker jelly consumed during the first 3 d of larval development typically contains flavonols at very low levels, however. RNA-Seq analysis of gene expression in neonates reared for three days on diets with and without quercetin revealed that, in addition to up-regulating multiple detoxifying P450 genes, quercetin is a negative transcriptional regulator of mitochondrion-related nuclear genes and genes encoding subunits of complexes I, III, IV, and V in the oxidative phosphorylation pathway. Thus, a consequence of inefficient metabolism of this phytochemical may be compromised energy production. Several P450s metabolize quercetin in adult workers. Docking in silico of 121 pesticide contaminants of American hives into the active pocket of CYP9Q1, a broadly substrate-specific P450 with high quercetin-metabolizing activity, identified six triazole fungicides, all fungal P450 inhibitors, that dock in the catalytic site. In adults fed combinations of quercetin and the triazole myclobutanil, the expression of five of six mitochondrion-related nuclear genes was down-regulated. Midgut metabolism assays verified that adult bees consuming quercetin with myclobutanil metabolized less quercetin and produced less thoracic ATP, the energy source for flight muscles. Although fungicides lack acute toxicity, they may influence bee health by interfering with quercetin detoxification, thereby compromising mitochondrial regeneration and ATP production. Thus, agricultural use of triazole fungicides may put bees at risk of being unable to extract sufficient energy from their natural food.

Synergistic interactions between a variety of insecticides and an ergosterol biosynthesis inhibitor fungicide in dietary exposures of bumble bees (Bombus terrestris L.)

“…In honey bees, prochloraz synergises both pyrethroid and pyrazole insecticides, and thiamethoxam (a neonicotinoid insecticide) is synergised by both tebuconazole and boscalid . Fungicides that synergise the toxicity of insecticides in honey bees act by inhibiting detoxification systems, such as the P450 enzyme complex . Taken together with previous work, our results suggest that the P450s could play an important role in both honey bees and bumble bees in the detoxification of a chemically varied group of active ingredients from three chemical families, namely the phenylpyrazoles (i.e.…”

Comparative transcriptome analysis on the synthesis pathway of honey bee (Apis mellifera) mandibular gland secretions

“…However, profiling the expression pattern of CYP450s in different organs and developmental stages can shed light on their specific functions 39, 40 .…”

Impacts of Dietary Phytochemicals in the Presence and Absence of Pesticides on Longevity of Honey Bees (Apis mellifera)

“…LLC., St. Louis, MO, USA) treatment (Qc), 0.5 mM p -coumaric acid and 0.25 mM quercetin-combined (PQ), and no phytochemicals (Control, CD). The phytochemical concentrations selected for testing in this work, also used in previous studies [2,25], were designed to fit within the range of concentrations ingested by worker bees over the course of their adult lives. Phytochemical concentrations vary in honey bee diets depending on plant species, tissue type, season, and geographic locality.…”