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Uncovering the drivers of antimicrobial resistance in wildlife through time and space at the University of Edinburgh

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Date & time Nov 22
Ends on Nov 29
Location
The University of Edinburgh, United Kingdom
Creator gwaters
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Uncovering the drivers of antimicrobial resistance in wildlife through time and space at the University of Edinburgh

What is the impact of human antibiotic use on antimicrobial resistance (AMR) of wild animals from around the world? How did AMR change through time since the advent of antibiotic mass production?


Apply by Thursday January 06 2022 at 12.00


Registration website


 

Project background


Antimicrobial resistance (AMR) is a major threat for human health worldwide and poses a significant financial burden in treatment costs. AMR is also a crucial issue in agriculture and livestock health. In addition, because antimicrobial resistance is a normal function of natural environments, wild animals carry resistance bacteria.

Mounting evidence exists for the exchange of resistant bacteria and their genes between wildlife, livestock, and humans. Yet, due to a number of key limitations, we know very little about the role of wild animals in the global dynamic of maintenance and spread of AMR.

First, because resistance bacteria and their genes are easily spread even to the most remote regions, we lack a baseline for AMR that is unaffected by human-made antibiotics. Second, we do not know how AMR load changed following the advent of industrial-scale antibiotic production, which started in the 1940s. We also lack comparative data to evaluate how local policies may affect AMR load in wildlife. Finally, we do not have a good understanding which wild animal species are more likely to carry a high AMR load. Taken together, we are missing crucial information for understanding global AMR dynamics and for devising efficient measure to reduce AMR spread among humans, environment and wildlife.

This project will use ancient metagenomics of preserved host-associated microbiomes to quantify AMR load and characterize the diversity of antibiotic resistance genes (ARGs) in wild animals from 100 years ago and until today. By identifying key ecological characteristics of wild animals that increase their exposure to antibiotics, it will propose sentinel species for efficient monitoring of environmental contamination. Spatial and temporal comparisons will highlight governmental policies that are successful in minimizing AMR spill-over into the environment. Going back in time, the project will allow the quantification of the impact of recent developments, both positive (e.g. restrictive use of antibiotics in medicine) and negative (e.g. spillage of untreated sewage) on the AMR load. Building on the One Health concept, this project will provide an integrative view of the progression and dynamics of antimicrobial resistance.



Research questions


The precise questions depend on the student's ideas and interests. Potential topics include:


  1. Evaluating how species ecology affects baseline AMR load and ARG diversity in wild animals using samples that have been collected prior to the advent of antibiotic mass production in 1940s

  1. Understanding how species ecology/lifestyle and exposure to humans and human-modified landscapes influence prevalence and diversity of ARGs in different wild mammals today

  1. Studying how national policies of antibiotic use and diversity of utilised antibiotic classes affect the AMR load and ARG diversity in wildlife in different parts of the world

  1. Characterising how changes in antibiotic production and use during the last 80 years since the advent of antibiotic mass production have affected the prevalence and diversity of ARGs in wildlife


Methodology


This project uses a unique, recently developed ancient metagenomics approach to study AMR from dental calculus. Dental calculus is a calcified host-associated oral microbiome that preserves on mammalian teeth, remains virtually unchanged through time, and can be collected from museum specimens. It thus represents a microbial fossil that provides a (genomic) view into the past. With this tool, the project will study in a comparative manner AMR across different host species from various parts of the world and through time, going back to before the advent of industrial-scale antibiotic production.



Dental calculus samples from museum specimens of several mammalian species are already available to the project. Additional samples will be collected from select species spanning the entire history of human antibiotic use (i.e. going back in time at least 80 years). The project will use shotgun metagenomics, which allows the characterisation of the entire DNA content of a complex sample. ARGs will be identified using available databases and predicted de novo. This project has both wet-lab and bioinformatics components.



 

Year 1:

Training in the required ancient DNA and computational techniques, sample collection and processing, sequencing and analyses of metagenomics data.


Year 2:

Possibly additional sample collection and data generation (e.g. for Topic 4), continue analyses and start preparing first set of manuscripts.


Year 3:

Finalise analyses, write manuscripts, disseminate results



Training


A comprehensive training programme will be provided comprising both specialist scientific training and generic transferable and professional skills.


The student will undertake training in the use of ancient DNA wet lab techniques and the analysis of ancient metagenomic sequencing data.



Requirements


Applicants should have at least an upper 2.1 degree in a relevant subject (evolutionary or computational biology or a related field), be highly motivated with a keen interest for large-scale metagenomics. Previous experience in bioinformatics, metagenomics, ancient DNA wet and/or dry lab would be an advantage.



References


Brealey JC, Leitão HG, Hofstede T, Kalthoff DC, Guschanski K. 2021. The oral microbiota of wild bears in Sweden reflects the history of antibiotic use by humans. Curr Biol 31: 1–9.


Brealey JC, Leitão HG, Van der Valk T, Xu W, Bougiouri K, Dalén L, Guschanski K. 2020. Dental calculus as a tool to study the evolution of the mammalian oral microbiome. Mol Biol Evol 37: 3003–3022.


Fellows Yates JA, Velsko IM, Aron F, Posth C, Hofman CA, Austin RM, Parker CE, Mann AE, Nägele K, Arthur KW, et al. 2021. The evolution and changing ecology of the African hominid oral microbiome. Proc Natl Acad Sci U S A118.


Warinner C, Rodrigues JFM, Vyas R, Trachsel C, Shved N, Grossmann J, Radini A, Hancock Y, Tito RY, Fiddyment S, et al. 2014.


Pathogens and host immunity in the ancient human oral cavity. Nat Genet 46: 336–44.


Subbiah M, Caudell MA, Mair C, Davis MA, Matthews L, Quinlan RJ, Quinlan MB, Lyimo B, Buza J, Keyyu J, et al. 2020. Antimicrobial resistant enteric bacteria are widely distributed amongst people, animals and the environment in Tanzania. Nat Commun 11: 228.


Pärnänen KMM, Narciso-Da-Rocha C, Kneis D, Berendonk TU, Cacace D, Do TT, Elpers C, Fatta-Kassinos D, Henriques I, Jaeger T, et al. 2019. Antibiotic resistance in European wastewater treatment plants mirrors the pattern of clinical antibiotic resistance prevalence. Sci Adv 5.



Supervisors


Katerina Guschanski

School of Biological Sciences

[email protected]

www.research.ed.ac.uk/en/persons/katerina-guschanski


Mick Watson

Roslin

[email protected]

 

Luke McNally

School of Biological Sciences

[email protected]

lukemcnally.wordpress.com/

 


E4 supervisors are happy to hear from candidates who would wish to adapt the project to their own ideas and research background.




How to apply


Please find all relevant information, application forms and instructions for referees via -

https://www.ed.ac.uk/e4-dtp/how-to-apply/application-process

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