Antimicrobial Resistance Research

Research on antimicrobial resistance has a focus on resistance in agriculture and the environment. We tackle AMR at all scales, from molecular mechanisms through to whole farm systems.

This includes research on resistance to transition metals, especially copper and zinc that are widely used in agriculture, including biomolecular interactions, genetic mechanisms, and models for co-selection. Our work on AMR in agriculture includes research on dairy slurry, slurry-amended soil, chicken litter, pig carcasses, and waste from sheep and beef herds. We also study virulence mechanisms (including gene regulation and biofilm formation) of clinically-relevant AMR bacteria, and potential alternative targets for therapeutics.

In addition we study the predatory bacterium Bdellovibrio bacteriovorus, both to understand its predatory lifecycle during which it consumes AMR bacteria as prey, and the potential of Bdellovibrio as an alternative therapeutic to conventional antibiotics. The outcomes of this research support national and global efforts to reduce the threat of AMR to human, animal and environmental health, from the use of antibiotics in agriculture.


Key aims and expertise

We take a highly interdisciplinary approach to antimicrobial resistance, making use of key facilities, including the on-site university of Nottingham dairy farm, and local waste water treatment plants, as well as national facilities at the Research Complex at Harwell. Our research includes traditional microbiological culturing techniques, modern genomics and metagenomics using short and long read platforms, microscopy, structural biology, mathematical models of microbial populations and complex microbiomes, and classical and Bayesian inference methods for fitting models to data.

Current projects

  • BBSRC £1.0M (2019-2023). AMR in Argentine Broiler Poultry Systems: Risks and Mitigation. Helen West (PI), Dov Stekel and collaborators at the Universities of Leeds and Lincoln, CEH and Argentina.

  • Medical Research Foundation (2017-2023) £4M. The Medical Research Foundation National Antimicrobial Resistance PhD Programme. With Matthew Avison (PI; Bristol) and 9 others. Supporting two PhD students in Nottingham.

Recent papers

Hooton SP, Pritchard AC, Asiani K, Gray-Hammerton CJ, Stekel DJ, Crossman LC, Millard AD and Hobman JL. 2021. Laboratory stock variants of the archetype silver resistance plasmid pMG101 demonstrate plasmid fusion, loss of transmissibility and transposition of Tn7/pco/sil into the host chromosome. Frontiers in Microbiology doi: 10.3389/fmicb.2021.723322

 Arya S, Williams A, Vazquez Reina S, Knapp CW, Kreft J-U, Hobman JL and Stekel DJ 2021. Towards a general model for predicting minimal metal concentrations co-selecting for antibiotic resistance plasmids. Environmental Pollution 275: 116602.

 Doidge C, West H, Kaler J. Antimicrobial Resistance Patterns of Escherichia coli Isolated from Sheep and Beef Farms in England and Wales: A Comparison of Disk Diffusion Interpretation Methods. Antibiotics (Basel). 2021 Apr 16;10(4):453. doi: 10.3390/antibiotics10040453. PMID: 33923678; PMCID: PMC8073771.

 Arya S, Todman H, Baker M, Hooton S, Millard A, Kreft JU, Hobman JL and Stekel DJ. 2020. A generalised model for generalised transduction: the importance of co-evolution and stochasticity in phage mediated antimicrobial resistance transfer. FEMS Microbiology Ecology: fiaa100.

Antibiotic and Metal Resistance in Escherichia coli Isolated from Pig Slaughterhouses in the United Kingdom
H Yang, SH Wei, JL Hobman, CER Dodd 2020
Antibiotics 9 (11), 746

 L. Hobley, J.K. Summers, R. Till, D.S. Milner, R.J. Atterbury, A. Stroud, M.J. Capeness, S. Gray, A. Leidenroth, C. Lambert, I. Connerton, J. Twycross, M. Baker, J. Tyson, J-U. Kreft, R.E. Sockett. (2020) “Dual predation by bacteriophage and Bdellovibrio can eradicate E. coli prey in situations where single predation cannot.” Journal of Bacteriology DOI: 10.1128/JB.00629-19

Research team

 

Research images

 

Figure 1
Figure 1 

Structures of the chaperone protein SilF A) apo B) Ag(I) bound C) Cu(I) bound and D) overlay of the structures. Protein X-ray crystallography was used to determined these structures and resolutions of 1.7-2.4 Angstroms were attained.

 

 
Figure 2
Figure 2. 

The structure of the outer membrane protein SilC determined by X-ray crystallography. The protein forms a trimer with a beta-barrel embedded in the membrane and an alpha helical barrel protruding into the periplasmic space

 
Figure 3
Figure 3 

Infographic showing drivers of antimicrobial resistance in dairy slurry and consequent environmental risks through spreading on land. 

 
Figure 4
Figure 4 

Schematic of mathematical model describing spread of antimicrobial resistance by lytic phages. The model includes phage-host population dynamics (red), phage-host co-evolution as bacteria evolve phage resistance and phage evolve to avoid it (blue), and generalized transduction of ARGs (green).   

 
Figure 5

Figure 5
Generic image for page showing Antibiotic Sensitivity analysis of an E. coli strain from the Sutton Bonington Dairy Farm.

 
Figure 6

Figure 6
Lifecycle of the predatory bacterium Bdellovibrio bacteriovorus. Bdellovibrio grows within the periplasm of prey bacteria, using the prey cell contents as nutrients for cell growth and replication. Bdellovibrio consumes a variety of Gram-negative AMR bacteria, giving rise to its potential use as an alternative to conventional antibiotics.

 

 

Antimicrobial Resistance Research

The University of Nottingham
Gateway Building, Sutton Bonington Campus
Loughborough, LE12 5RD


telephone: +44 (0) 115 951 6257
email:sacha.mooney@nottingham.ac.uk