Bees, bugs and antibiotics -the interactions of veterinary and agricultural antibiotics with the gut microbiome, resistome and health of bees
Lead Research Organisation:
University of Exeter
Department Name: Biosciences
Abstract
Bee pollination services are crucial for agricultural sustainability. It has recently become clear that the gut microbiome plays a crucial role in bee health. In fact, the resistance against Critihidia bombi, a key bumblebee parasite, is predominantly explained by the gut biome rather than by the host itself (Koch et al Ecology Letters 2012, Wilfert et al. Molecular Ecology 2007). Antibiotics can disrupt this interaction and cause fitness loss (Koch et al. PNAS 2011). Environmental exposure to antibiotics is a potentially serious problem in bees: beyond environmental contamination, antibiotic sprays are used when crops such as apples and pears are in flower and prophylactic antibiotic treatment of honeybees is widespread in North America. While this treatment is currently not licensed in Europe, intensification of commercial pollination services and the rising pathogen pressure in bumblebees and honeybees are likely to make this an attractive option to commercial pollination service providers. Studying the interactions of pollinators, pathogens and antibiotics is thus crucial for sustainable agricultural intensification.
We propose to use an interdisciplinary approach to study the importance of environmental antibiotics for bee health and the spread of antimicrobial resistance, combining experimental approaches, genomics and mathematical modelling to study sublethal effects of antibiotics on microbiome diversity, the evolution of antimicrobial resistance, and host fitness. In the first rotation project (Gaze lab, Exeter Medical School), the student will use bioinformatics to study changes in the microbiome under conventional and environmentally enhanced agricultural schemes (transcriptomic data from LW's ongoing BBSRC grant, complemented with an experimental data set of bumblebees exposed/unexposed to antibiotics). The student will experimentally test whether environmental levels of antibiotics reduce pathogen resistance and bumblebee fitness. This work will also assess whether selection for antimicrobial resistance (AMR) occurs in the bumblebee gut.
We propose to use an interdisciplinary approach to study the importance of environmental antibiotics for bee health and the spread of antimicrobial resistance, combining experimental approaches, genomics and mathematical modelling to study sublethal effects of antibiotics on microbiome diversity, the evolution of antimicrobial resistance, and host fitness. In the first rotation project (Gaze lab, Exeter Medical School), the student will use bioinformatics to study changes in the microbiome under conventional and environmentally enhanced agricultural schemes (transcriptomic data from LW's ongoing BBSRC grant, complemented with an experimental data set of bumblebees exposed/unexposed to antibiotics). The student will experimentally test whether environmental levels of antibiotics reduce pathogen resistance and bumblebee fitness. This work will also assess whether selection for antimicrobial resistance (AMR) occurs in the bumblebee gut.
| Description | Gut microbiome disequilibrium is increasingly being associated with host fitness reductions, including for the economically important and disease-challenged western honey bee, Apis mellifera. In lab experiments the antibiotic tetracycline, which is used to prevent American Foulbrood Disease in countries including the US, elevates honey bee mortality by disturbing the microbiome. It is unclear however, how this elevated individual mortality affects colony level fitness. We used an agent-based model (BEEHAVE) and empirical data to assess colony level effects of antibiotic-induced worker bee mortality, by measuring colony size. We investigated whether there is a dose-response relationship between the duration that the antibiotic-induced mortality probability is imposed for, and colony failure or colony size. The dose-response model revealed that colony failure can be induced if the antibiotic-induced mortality persists for 120 days per year. Moreover, we found that when simulating antibiotic-induced mortality of worker bees from just 60 days per year, up to a permanent effect, the colony is reduced to such a degree that tetracycline treatment would not meet the European Food Safety Authority's honey bee protection goals. When antibiotic mortality was only imposed for the hypothetical minimal exposure time, which assumes that antibiotics are active only during the recommended treatment period of fifteen days in spring and fifteen days in autumn, the colony fitness reduction was only marginally under the European Food Safety Authority's threshold. Modelling colony level impacts of antibiotic treatment shows that individual worker mortality caused by antibiotics can lead to colony mortality. To assess the full impact of antibiotic treatments on honey bee hive mortality, the persistence of antibiotic induced mortality will have to be determined experimentally, in vivo. In the meantime, the recommendation from this work is to limit the prophylactic use of antibiotics in honey bees and to not exceed the recommended treatment strategy as excess use of antibiotics is likely to lead to a decrease in colony growth and an increase in colony mortality. It is imperative that we attempt to understand the anthropogenic expansion of antibiotic resistance gene (ARG) reservoirs, which can be accessed by pathogens. Humans' contamination of the environment with antibiotics puts immense pressure on non-target bacteria, for example in gut microbiomes of organisms exposed to contamination, to evolve or acquire antibiotic resistance genes. Application of Streptomycin to blossoming apple and pear orchards (to treat fire blight) is one route of environmental contamination, which temporally coincides with the emergence of corbiculate bee queens. In this study, Taqman ® qPCR was used to uncover that exposure to an agriculturally relevant therapeutic dose (50 µg/ml) of Streptomycin causes an 88% reduction of bacterial cells (16s rRNA copies) within the gut microbiome of the buff-tailed bumble bee (Bombus terrestris), which did not recover after 5 days. Conversely, Streptomycin exposure did not increase the prevalence of two indicators of mobile antibiotic resistance genes: Int1 and IS1133. Finally, through culture-based methods, I determined that the minimum inhibitory concentration of Streptomycin for the culturable microbiome was ~ 15.6 µg/ml and that the culturable microbiome was entirely wiped out by Streptomycin exposure. Streptomycin clearly exerts a huge selection pressure on the gut microbiome, however it is not yet clear if B. terrestris can act as reservoirs and disseminators of ARGs. Based on the results acquired here, future studies that should be undertaken to further our understanding of this system have been recommended. |
| Exploitation Route | Others may use the results of the BEEHAVE modelling experiment to add to the body of evidence regarding antibiotic treatment of honey bees. This could be important in policy outcomes for antibiotic use in apiculture and thus impact on bee health. Moreover, others may use our rigorous bootstrap method when inputting new parameters to the BEEHAE model to generate predictive distributions of the model outputs. We believe this is very important when using large, modular ecological models which are parametised with data from multiple different sources. |
| Sectors | Agriculture, Food and Drink,Environment,Pharmaceuticals and Medical Biotechnology |
| Description | Junior Scientist Travel Grant (non GS Meeting) |
| Amount | £750 (GBP) |
| Organisation | The Genetics Society |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 08/2018 |
| End | 08/2018 |
| Description | National AMR Training Programme |
| Organisation | Foundation for Medical Research (FRM) |
| Country | France |
| Sector | Charity/Non Profit |
| PI Contribution | I have presented my research at their annual conference. I also attended their residential training course in August 2019 as one of 54 attendees. |
| Collaborator Contribution | (Description largely from MRF blurb of the training week) They put on a training week where we heard contributions from experts in the field from a range of disciplines; learnt about the problem of AMR from a practitioners' perspective (e.g. clinicians working in primary care, secondary care, global health and vets working in livestock production etc) and what they need to help tackle AMR; how academics from different disciplines are helping to tackle AMR in a cross-disciplinary way; undertook a workshop on social science/ethnographic/humanities approaches to tackling the global challenge of AMR, and went on site visits. Additionally, we worked in an interdisciplinary team of 6 students to develop a training output in response to a challenge around AMR. We worked in an area which is not the topic of our PhD but we helped and inform others in the team based on our own expertise. Our output was a written an article for the press, a policy document, a briefing for a government minister etc and we were trained by journalists, policy development experts and stakeholders. Finally, we gave a short presentation on the final day and submitted our finished article the following week for judging (and potential publication). Overall, the week's activities offered an excellent networking opportunity where you can discuss your work with others who have similar and very different perspectives on the same problem. |
| Impact | Increased my netwrok. |
| Start Year | 2018 |
| Description | Cafe Sci |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | Blurb: Battling superbugs An introduction to antibiotic resistance and gene transfer in the environment. with David Walker-Sünderhauf, Ellinor Alseth, Laura Bulson Fears of antibiotic resistance, prompted by over prescription for humans and animals alike. What is the science behind this perpetual arms race between humans and the world of bacteria? What are new approaches against such superbugs? Three postgraduates at the University of Exeter talk about their research on phage therapy and biotechnology. In this talk, I discussed the role of the environment as a reserviour for antibiotic resistance genes, and discussed my research with regards to the potential for wild animals to act as mobile reserviours of antibiotic resistance. We then led a panel discussion where the general public, many of whom were doctors or school teachers, asked us their questions. The aim was to engage the public and encourage them to act as stewards of antibiotics. After the talk we were invited to visit a local school and speak to the students about our research to both inform them of the antibiotic resistance crisis, and encourage them to become interested in STEM. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Royal Cornwall Show - stall about antibiotic resistance |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | We had a stool at the Royal Cornwall Show where we had a small workshop for children to learn about antibiotic resistance and bacteria through play with playdough and beads. We found that parents were also very engaged with these topics and asked lots of questions. We also had activities for older children and adults where they were asked to rank the environments that they thought would contain the most antibiotic resistant bacteria. |
| Year(s) Of Engagement Activity | 2019 |