Unraveling the Metabolic Interplay Between the Honeybee Gut Microbiota and a Comprehensive Pesticide Library

• Applicant: Dr. Michael Zimmermann, Ph.D.
• Subject Area: Ecology and Biodiversity of Animals and Ecosystems, Organismic Interactions ; Microbial Ecology and Applied Microbiology ; Ecology of Land Use
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 531017192

Bees are key pollinators in agriculture and natural ecosystems suffering serious population declines. In addition to habitat shrinkage and pathogen infections, pesticides are one of the key stressors affecting bee health. While incidences of bee mortality linked to acute pesticide exposure are well studied, chronic, sub-lethal pesticide exposure has now been shown to depress immunocompetence, pathogen resistance, and foraging behavior in bees. These same traits are modulated by the microbial communities in the gut of social bees. Therefore, understanding the mechanistic interplay between pesticides, bees and their microbiota is crucial to estimate the impact of chronic, sub-lethal pesticide exposure, common across diverse ecosystems. Limited findings indicate that the honeybee gut microbiota is both perturbed by certain pesticides, while also biochemically altering others. We propose an innovative, collaborative research program to elucidate the interplay between a wide range of pesticides, the gut microbiota, and bee health. Our overarching hypothesis is that the gut microbiota of bees interacts with many pesticides in a reciprocal manner. A significant fraction of pesticides induce toxic dysbiosis, while microbes, in turn, biochemically metabolize others. These interactions shape the bee’s health and create long-term evolutionary pressure towards resistance against pesticides, possibly resulting in cross-resistance or cross-sensitization to other xenobiotics and unforeseen effects on bee health. In three complimentary work packages, we will i) systematically document, in vitro, the interactions between 1054 pesticides, antibiotics and other xenobiotic compounds and the bee microbiota, ii) identify how those interactions affect bee health, and iii) investigate whether long-term pesticide exposure leads to cross-resistance against different pesticides and antibiotics. We will provide unprecedented insight into microbial interactions with toxic pesticides and subsequent effects on their host. The unique, albeit complimentary, capabilities of the Engel and Zimmermann labs enable us to design bottom-up, in vitro screens of bacteria versus a broad library of pesticides. Once we have identified the pesticides that significantly interact with the bee gut microbiota, we can validate our results with in vivo experiments. This design is feasible thanks to established protocols employing advanced liquid handling robotics, high-throughput mass spectrometry, a well-established apiary and bee lab, and extensive libraries of both bee gut isolates and pesticide standards. Our results have high potential to 1) advance understanding of microbiota-mediated pesticide impacts on bee health, 2) identify novel mechanisms of pesticide resistance and biotransformation, 3) understand the scope of evolved cross-resistance resulting from exposure to xenobiotic compounds, and 4) guide public policy regarding pesticide usage.

• DFG Programme: Research Grants
• International Connection: Switzerland
• Cooperation Partner: Professor Dr. Philipp Engel