Oral Presentation Australian Society for Microbiology Annual Scientific Meeting 2019

Designing peptide polymers as antibiotic adjuvants for multidrug resistant bacteria (#74)

Neil O'Brien-Simpson 1 , Wenyi Li 1 , Shu J Lam 2 , Edgar H H. Wong 2 , Jason C Lenzo 1 , James A Holder 1 , Greg G Qiao 2 , Eric C Renolds 1
  1. ACTV Research Group, Melbourne Dental School and The Bio21 Institute , The University of Melbourne, Parkville, VIC, Australia
  2. Polymer Science Group, Department of Chemical & Biomolecular Engineering, The University of Melbourne, Parkville, VIC, Australia

The continuing rise in antibiotic and multi-drug resistant bacterial infections is a major global medical health issue, which is not being met by traditional antibiotic research. Here, we show that a new class of antimicrobial agents, termed ‘Structurally Nanoengineered Antimicrobial Polypeptide Particles’ (SNAPPs), synthesized using ring-opening polymerization (ROP) of α-amino acid N-carboxyanhydrides (NCAs) to produce star-shaped polypeptide nanoparticles exhibit antibiotic-adjuvant properties resulting in colistin-multi-drug resistant (CMDR) bacteria becoming sensitive to antibiotics once more. Synergistic interactions were demonstrated between a model SNAPP and ampicillin, imipenem, doxycycline, gentamicin, or silver ions. We show that different peptide architectures alter the activity of the SNAPPs. We also show that the effective antibiotic dose could be decreased by 3.7 to 16 fold from the original lethal dose while retaining synergistic interactions with SNAPPs against CMDR bacteria. Further, we demonstrate that the combination treatment approach using SNAPPs is able to attenuate toxicity. Interestingly, our studies show that SNAPPs sensitise bacteria to antibiotics that were previously ineffective. Overall, this study demonstrates the potential of synergistic combinations of SNAPPs with conventional antibiotics where the SNAPP not only has antimicrobial activity in its own right but also acts as an adjuvant for the conventional antibiotic to treat CMDR bacterial infections.