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

This PhD opportunity is being offered as part of the LSTM and Lancaster University Doctoral Training Partnership. Find out more about the studentships and how to apply.

Abstract

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 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. An over arching aim of the project is to confirm the predicted no effect concentrations (PNECs) of clinically relevant antibiotics using the multi-replicon system which will represent the first time this has been done at the sub-cellular, molecular scale.

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

Goodman RN, Tansirichaiya S, Roberts AP. Development of pBACpAK entrapment vector derivatives to detect intracellular transfer of mobile genetic elements within chloramphenicol resistant bacterial isolates. J Microbiol Methods. 2023 Aug 28:106813. doi: 10.1016/j.mimet.2023.106813. Epub ahead of print. PMID: 37647945.

Cocker D, Chidziwisano K, Mphasa M, Mwapasa T, Lewis JM, Rowlingson B, Sammarro M, Bakali W, Salifu C, Zuza A, Charles M, Mandula T, Maiden V, Amos S, Jacob ST, Kajumbula H, Mugisha L, Musoke D, Byrne R, Edwards T, Lester R, Elviss N, Roberts AP, Singer AC, Jewell C, Morse T, Feasey NA. Investigating One Health risks for human colonisation with extended spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae in Malawian households: a longitudinal cohort study. Lancet Microbe. 2023 Jul;4(7):e534-e543. doi: 10.1016/S2666-5247(23)00062-9. Epub 2023 May 16. PMID: 37207684; PMCID: PMC10319635.

Goodman RN, Tansirichaiya S, Brouwer MSM, Roberts AP. Intracellular Transposition of Mobile Genetic Elements Associated with the Colistin Resistance Gene mcr-1. Microbiol Spectr. 2023 Feb 14;11(1):e0327822. doi: 10.1128/spectrum.03278-22. Epub 2022 Dec 13. PMID: 36511714; PMCID: PMC9927407.

Tansirichaiya S, Goodman RN, Guo X, Bulgasim I, Samuelsen Ø, Al-Haroni M, Roberts AP. Intracellular Transposition and Capture of Mobile Genetic Elements following Intercellular Conjugation of Multidrug Resistance Conjugative Plasmids from Clinical Enterobacteriaceae Isolates. Microbiol Spectr. 2022 Feb 23;10(1):e0214021. doi: 10.1128/spectrum.02140-21. Epub 2022 Jan 19. PMID: 35044219; PMCID: PMC8768599.

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.