Engineering nano particulate anti-virulence compounds for synergy with other antimicrobials

Project description

The development of antibiotic resistance, and in particular multi-drug resistant (MDR) pathogens, threatens to send us back to a time when antibiotics were not available. Thus, engineering new antimicrobials or formulations, with novel mechanisms of action (MOA), against which development of antimicrobial resistance (AMR) is unlikely, is a significant global area of interest. Antivirulence agents, are exciting new ways to achieve this goal. These agents disarm bacteria, without killing them, and thus exert low selective pressure for the development of AMR. This approach offers many advantages, such as improved potency, spectrum and capacity to kill MDR organisms when combined with other antimicrobials, and provides a means to target other species to bacteria.

Herein, we aim to identify and develop novel, potent, reversible antivirulence agents and their beneficial combinations with other antimicrobial agents, with a goal to progress these towards the clinic. This will include the rational design of peptide-based antivirulence agents, and their fusions with other antimicrobial species, to provide synergy, as well as reduce associated costs, off-target effects, toxicity and the potential for AMR development. Nanoformulations and polymers will be produced to enable engineering of size, shape and surface properties, to provide boundless opportunities to tune these systems biofilm targeting and permeation properties, with the developed systems assessed against libraries of important disease associated microbes and models. Finally, the fusion species developed herein, will offer the potential for these species to be genetically encoded or synthetically produced, opening opportunities in food production (e.g. as biopreservatives), materials science (biofilm resistant surfaces), veterinary science (improved nutrition) amongst other applications, and will provide a valuable intellectual property platform.

Outcomes

• The training of a student in the development of antimicrobials, drug formulation approaches and their assessment. These skills will prove important for the development of urgently needed new antimicrobial therapies to overcome antibiotic resistance.
• Identification of combinations of antivirulence and antimicrobial agents that provide synergy, and are safe and effective for development as new treatments for disease-associated bacteria, with an aim to progress these to the clinic.
• Identification of nanoformulations of these species, which provide enhanced activity against biofilms, which are hard to treat with current antimicrobial formulations, and affect many industries including health and food production.
• The outcomes of this project are commercially valuable, and would represent an exciting intellectual property platform, which could be used to develop new antimicrobial formulations for the market, as well as enhancing the activity of antimicrobials against which resistance has developed.

Essential capabilities

Training in sciences – especially biological, chemical and pharmaceutical sciences.

Desireable capabilities

Experience in relevant areas e.g. microbiology, drug formulation, biotechnology, chemistry, materials science. Lab experience would be favourable.

Expected qualifications (Course/Degrees etc.)

Science, Biotechnology, Engineering, or Pharmacy/Pharmaceutical Sciences qualifications for PhD study.

Additional information for applicants

note: i-students must have own scholarship to apply (CSIR, UCG-NET, etc)

Candidate Discipline

antimicrobial resistance nanomedicine formulation synergy.