Project No.2243

Primary Supervisor

Dr Jose Ortega-Roldan – University of Kent

Co-Supervisor(s)

Dr Jennifer Hiscock – University of Kent

Dr Neil Wells- University of Southampton

Dr Charlotte Hind – Public Health England (PHE)

Summary

This project will develop a new, integrative, in-cell methodology exploiting the atomic detail of solution Nuclear Magnetic Resonance (NMR) spectroscopy, to tackle the challenges which currently limit antimicrobial development.

Supramolecular Self-associating Amphiphiles (SSAs) are a new class of ≈ 100 surface active antimicrobial agents and antibiotic/biocide efficacy enhancers invented by JH.

Project aim: To develop a suite of novel high-throughput methods using a bioreactor coupled to an NMR spectrometer, that will enable us to derive the mechanism of action for this technological innovation on the atomic level.

These studies will be validated through the use of complimentary nanodisc studies (references 3 and 4) and microbiological techniques against multidrug resistant ESKAPE pathogens (CH).

Objectives:
1. Optimise NMR methods to monitor SSA internalisation.
2. Detection of molecular structural alterations upon interaction with bacteria.
3. Monitoring metabolic changes of the bacteria in the presence of antimicrobial agents.
4. Determination of resistance mechanisms at the metabolic level.
5. Development of next-generation SSAs with enhanced antimicrobial/efficacy enhancement properties based on the experimental data generated.

JOR lab:
• Develop/optimize NMR assays in cells (Objectives 1, 3,4).
• Test initial set of SSA molecules to elucidate their influx/efflux rates and effect on cells (Objectives 1, 3).
• Test potential resistance mechanisms against SSAs (Objective 4).

Dr Jennifer Hiscock Lab:
• Synthesis and design of iterative generations of SSAs (Objectives 2-5).

Dr Neil Wells Lab:
• Elucidation of the structural changes of SSAs upon interaction with biological membranes (Objective 2).

Dr Charlotte Hind Lab:
• Determination of SSA efficacy against multidrug resistant ESKAPE pathogens (Objective 5).

Impact areas:
1. Health – better antimicrobial treatments/commercial decontamination products.
2. Bioeconomy – Commercialisation of SSA technology.
3. People and talent – Support of women and other marginalised groups within STEM – See later sections for detail.