2024-25 Project (Lindsay & Knight)

Antimicrobial Resistance (AMR) gene transfer in Methicillin Resistant Staphylococcus aureus (MRSA): mechanisms and dynamics using clinical isolates

SUPERVISORY TEAM

Supervisor

Professor Jodi Lindsay at SGUL
Email: jlindsay@sgul.ac.uk

Co-Supervisor

Dr Gwenan Knight at LSHTM
Email: Gwen.Knight@lshtm.ac.uk

PROJECT SUMMARY

Project Summary

Antimicrobial resistance (AMR) is a growing global problem, that requires innovative, cross-disciplinary solutions. However, the dynamics and genetic mechanisms that underpin the transfer and stability of resistance genes within bacterial population is poorly understood.   In this project, we will use clinical strains of methicillin resistant Staphyloccocus aureus (MRSA), an important clinical pathogen, to measure and then characterise the genetic components behind gene transfer of resistance. Paired with bioinformatic analysis, and mathematical modelling, this project will have direct translational impact on clinical practice and will inform our understanding of the underlying evolutionary changes and how these can be optimally harnessed for AMR control.

Project Key Words

Antimicrobial resistance, MRSA, gene transfer, mathematical modelling

MRC LID Themes

  • Global Health = Yes
  • Health Data Science = Yes
  • Infectious Disease = Yes
  • Translational and Implementation Research = Yes

Skills

MRC Core Skills

  • Quantitative skills = Yes
  • Interdisciplinary skills = Yes
  • Whole organism physiology = Yes

Skills we expect a student to develop/acquire whilst pursuing this project

Antimicrobial resistance, microbiology, mathematical modelling

Routes

Which route/s is this project available for?

  • 1+4 = Yes
  • +4 = Yes

Possible Master’s programme options identified by supervisory team for 1+4 applicants:

  • LSHTM – MSc Medical Microbiology
  • SGUL – MRes Biomedical Science – Antimicrobial Resistance
  • SGUL – MRes Biomedical Science – Infection and Immunity

Full-time/Part-time Study

Is this project available for full-time study? Yes
Is this project available for part-time study? Yes

Eligibility/Requirements

Particular prior educational requirements for a student undertaking this project

  • SGUL’s standard institutional eligibility criteria for doctoral study.
  • Good undergraduate degree in biological sciences with laboratory experience.  Post-graduate research degree in microbiology, genetics or a quantitative field is an advantage.

Other useful information

  • Potential CASE conversion? = No

PROJECT IN MORE DETAIL

Scientific description of this research project

MRSA is the most common cause of AMR death, and affects all branches of human medicine.  In this project we will use microbiology and mathematical modelling techniques to investigate how clinical isolates exchange AMR genes, leading to infections that are harder to prevent and treat.  MRSA resistance genes are often carried on mobile genetic elements and transfer using endogenous bacteriophage.  We have built laboratory and mathematical models of transfer, incorporating antimicrobial exposure and using epidemiologically successful MRSA isolates.  The dynamics of gene exchange are complex, but improving our understanding of the drivers and barriers to AMR gene exchange and how they can be manipulated in evolving MRSA populations will lead to better targeted interventions.   

Project objectives
– Using newly discovered genes demonstrated to be involved in MRSA gene transfer, determine their distribution and role in gene transfer in a collection of epidemiologically successful vs unsuccessful MRSA
– Investigate environmental conditions or external interventions that control AMR gene transfer in clinical isolates 
– Model how genes and environmental interventions may contribute to AMR spread in MRSA populations.   

Techniques to be used
– Microbiology laboratory assays of AMR gene transfer, including confirmation using molecular methods  – Microbial bioinformatics 
– Mathematical modelling, building on established models.   

Resources 
– All of the methods, equipment and materials for this project are currently available in our laboratory.  This project is building on a series of successful MRC-LID DTP projects and an experienced team of supervisors, collaborators and externally funded projects. 
– MRSA laboratory with all assays and resources for studying and characterising resistance available at St George’s as well as data from past experiments 
– A comprehensive set of clinical MRSA isolates from the UK and Europe are already available and characterised with WGS. 
– Mathematical modelling framework, with training and support available within CMMID at LSHTM    

Potential risks  
–  There is currently limited grant funding in the laboratory to supplement the studentship. However, the experiments are inexpensive and fall easily within the stipend, and further grant applications are in progress.

Further reading

(Relevant preprints and/or open access articles)

  • 10.1016/j.ijmm.2013.11.010
  • 10.1128/msystems.00135-22

Additional information from the supervisory team

  • The supervisory team has provided a recording for prospective applicants who are interested in their project. This recording should be watched before any discussions begin with the supervisory team.
    Lindsay-Knight Recording
  • The strain collection we will use is here   10.1016/j.cmi.2023.05.015

MRC LID LINKS