Understanding mobility of antimicrobial resistance genes and associated mobile genetic elements in response to different antimicrobial selection pressures.

Intracellular transposition of AMR genes between replicons (plasmids and chromosomes) and intercellular conjugation between bacterial cells accounts for the majority of clinically relevant AMR acquisition and transmission events in the Enterobacteriaceae. We have a unique opportunity to align a PhD project with recent significant funding from the JPIAMR for the STRESST project, and from UKRI for the iiCON project (to Roberts and Feasey) which will sample hospital wastewater for AMR bacteria, and which aims to characterise the inter- and intracellular movement of selected AMR genes in response to antimicrobial residues in wastewater.

This PhD project will extend this work to determine the molecular aspects of the regulatory systems which control AMR gene and associated mobile genetic element mobility and determine how these systems respond to the presence of antimicrobials in the environment. The project will incorporate micro- and molecular biology techniques, bioinformatic analysis of whole genome sequences, and the determination of rates of horizontal gene transfer and intracellular transposition which will underpin mathematical models to predict the effects of antimicrobials within clinical and environmental niches.

Where does the project lie on the Translational Pathway?

T1 – Basic Research

Expected Outputs

Publications describing novel mobile genetic elements from bacteria isolated as part of our ongoing STRESST and iiCON studies.

Publications describing molecular mechanisms of transcriptional and translation regulation of mobile genetic elements in response to antibiotics

Publications describing mathematical models of AMR transfer in response to various antimicrobials

White paper to water industry stakeholders in year three via the STRESST project.

Input into policy dialogue on environmental contamination with antibiotic residues via both STRESST and iiCON.

Policy brief for AMR Technical Working Group for MoH, Malawi

Training Opportunities

Microbiology, molecular biology,  genomics and metagenomics supported by bioinformatics analysis and mathematical modelling.

Scientific communications & publications

Skills Required

A keen interest in translational research into the microbiology and molecular biology of antimicrobial resistance.

Key Publications associated with this project

Tansirichaiya S, Moyo SJ, Al-Haroni M, Roberts AP. Capture of a novel, antibiotic resistance encoding, mobile genetic element from Escherichia coli using a new entrapment vector. J Appl Microbiol. 2021 Mar;130(3):832-842. doi: 10.1111/jam.14837. Epub 2020 Sep 17. PMID: 32881179.

Lester R, Haigh K, Wood A, MacPherson EE, Maheswaran H, Bogue P, Hanger S, Kalizang'oma A, Srirathan V, Kulapani D, Mallewa J, Nyirenda M, Jewell CP, Heyderman R, Gordon M, Lalloo DG, Tolhurst R, Feasey NA. Sustained Reduction in Third-generation Cephalosporin Usage in Adult Inpatients Following Introduction of an Antimicrobial Stewardship Program in a Large, Urban Hospital in Malawi. Clin Infect Dis. 2020 Dec 3;71(9):e478-e486. doi: 10.1093/cid/ciaa162. PMID: 32060523; PMCID: PMC7713689.

Hubbard ATM, Mason J, Roberts P, Parry CM, Corless C, van Aartsen J, Howard A, Bulgasim I, Fraser AJ, Adams ER, Roberts AP, Edwards T. Piperacillin/tazobactam resistance in a clinical isolate of Escherichia coli due to IS26-mediated amplification of blaTEM-1B. Nat Commun. 2020 Oct 1;11(1):4915. doi: 10.1038/s41467-020-18668-2. PMID: 33004811; PMCID: PMC7530762.

Podnecky NL, Fredheim EGA, Kloos J, Sørum V, Primicerio R, Roberts AP, Rozen DE, Samuelsen Ø, Johnsen PJ. Conserved collateral antibiotic susceptibility networks in diverse clinical strains of Escherichia coli. Nat Commun. 2018 Sep 10;9(1):3673. doi: 10.1038/s41467-018-06143-y.

Seier-Petersen MA, Jasni A, Aarestrup FM, Vigre H, Mullany P, Roberts AP, Agersø Y. Effect of subinhibitory concentrations of four commonly used biocides on the conjugative transfer of Tn916 in Bacillus subtilis. J Antimicrob Chemother. 2014 Feb;69(2):343-8. doi: 10.1093/jac/dkt370.

Now Accepting Applications 

CLOSING DATE FOR APPLICATIONS: Application Portal closes: Wednesday 9th February 2022 (12:00 noon UK time)

Shortlisting complete by: End Feb/early March 2022

Interviews by: Late March/early April 2022

For more information on Eligibility, funding and how to apply please visit the MRC DTP/CASE pages