Understanding the rules of life

Bioscience for an integrated understanding of health

Category: Standard Studentships

The development of Supramolecular Self-associating Antimicrobials (SSAs) towards real world impact

Primary Supervisor

Prof Dan Mulvihill – University of Kent

Co-Supervisor(s)

Dr Jennifer Hiscock – University of Kent

Prof Jonathan Essex – University of Southampton

Prof Syma Khalid – University of Oxford

Summary

Supramolecular Self-associating Amphiphiles are a new class of molecule invented by J. Hiscock, and developed collaboratively with D. Mulvihill, which exhibit multifaceted antimicrobial functionality, and are now ready to be developed out of the lab to have a real world use with your help.

To date we have analysed the antimicrobial activity of ≈ 70 SSAs against Gram +ve MRSA and Gram -ve E. coli, discovering the following:

  • SSAs are presented to the microbial surface as self-associated aggregates, or self-associated hydrogel fibres, the properties and composition of which effects antimicrobial efficacy.
  • SSA aggregates adhere to the bacterial surface to form a coating. Additionally, the monomeric units of an SSA are capable of selectively interacting with specific phospholipids present at the bacterial cell surface.
  • The SSAs then permeate the cell membrane, entering the interior of the bacteria and interacting with cellular machinery.
  • SSAs can also enhance the activity of other antimicrobial agents.

Aims:

  1. Determine bulk membrane self-association and permeation processes for 10 lead SSAs.
  2. Characterise mode of antimicrobial action for these SSAs and determine suitability for commercialisation.
  3. Use project outputs to inform design of next genoration SSAs, increasing commercialisation potential.

Scientific approach:

D. Mulvihill lab:

  • Obtain MIC50 values for ESKAPE pathogens supported by Public Health England (Porton Down) (Aims 1, 3).
  • Ascertain the formulation of SSAs into household products to enable low cost entry of SSAs into the commercial sector (Aims 1, 3).
  • Undertake microscopy analysis to derive membrane permeation processes (Aim 2).

J. Hiscock Lab:

  • Synthesis and design of SSAs (Aims 1, 3).
  • To understand the physicochemical effects of current lead and next generation SSAs alone and co-formulated with commercial agents of interest (Aims 1, 3).

S. Khalid Lab (Aims 1, 2):

  • Use coarse-grained Molecular Dynamics to understand SSA bacterial surface interactions and initial stages of permeation.
  • Refine the SSA aggregates by converting into atomistic detail.

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, through supporting the international Women in Supramolecular Chemistry network www.womeninsuprachem.com.