Withdrawn 14th Australian Peptide Conference 2022

Star Peptide Polymers are Gram-positive Multi-Drug Resistant Bacteria Killers (#215)

Wenyi Li 1 , Sara Hadjigol 1 , Greg G. Qiao 1 , Neil O'Brien-Simpson 1 , Sadegh Shabani 1
  1. The University of Melbourne, Melbourne, VIC, Australia

Antibiotic resistance in bacteria, especially Gram-positive bacteria like Staphylococcus aureus, is gaining considerable momentum worldwide1. With few new antibiotics coming on the market2, there is a need for novel antimicrobial materials that target and kill multi-drug resistant (MDR) Gram-positive pathogens like MRSA.

We have previously developed a new class of star-shaped peptide mimetic polymers, termed “structurally nanoengineered antimicrobial peptide polymers” or “SNAPPs” using N-carboxyanhydride (NCA) ring opening polymerisation (ROP) of lysine and valine NCA monomers. SNAPPs were found to have superior antibacterial activity against Gram-negative pathogens compared to other materials (natural antimicrobial peptides), and were highly effective against MDR species both in vitro and in vivo 3,4. In this work, we investigated a novel antibacterial agent, the Star-Shaped “Structurally Nanoengineered Antimicrobial Peptide Polymers” (SNAPPs) with varying core size (denoted as SX) and increasing degree of arm length (small/S, medium/M, long/L, very-long/VL)5 against Gram-positive bacterial infections. Using a novel mixed-bacteria antimicrobial assay we show that the star-peptide polymers preferentially target and kill Gram-positive pathogens including MRSA. The structure of the star-peptide polymer was a major contributor to antimicrobial efficacy with an 8-armed star-structure inducing the greatest bactericidal activity. The different star-peptide polymer structures were also found to induce different mechanisms of bacterial death both in vitro and in vivo. These results highlight the potential utility of peptide/polymers to fabricate materials for therapeutic development against MDR Gram-positive bacterial infections.

  1. (1) Klein, E. Y.; Milkowska-Shibata, M.; Tseng, K. K.; Sharland, M.; Gandra, S.; Pulcini, C.; Laxminarayan, R. Assessment of WHO antibiotic consumption and access targets in 76 countries, 2000-15: an analysis of pharmaceutical sales data. Lancet Infect Dis 2021, 21 (1), 107.
  2. (2) Li, W.; Separovic, F.; O'Brien-Simpson, N. M.; Wade, J. D. Chemically modified and conjugated antimicrobial peptides against superbugs. Chem. Soc. Rev. 2021, 50 (8), 4932.
  3. (3) Lam, S. J.; O'Brien-Simpson, N. M.; Pantarat, N.; Sulistio, A.; Wong, E. H. H.; Chen, Y.-Y.; Lenzo, J. C.; Holden, J. A.; Blencowe, A.; Reynolds, E. C.et al. Combating multidrug-resistant Gram-negative bacteria with structurally nanoengineered antimicrobial peptide polymers. Nat. Microbiol. 2016, 1, 16162.
  4. (4) Lam, S. J.; Wong, E. H. H.; O’Brien-Simpson, N. M.; Pantarat, N.; Blencowe, A.; Reynolds, E. C.; Qiao, G. G. Bionano interaction study on antimicrobial star-shaped peptide polymer nanoparticles. ACS Appl. Mater. Interfaces 2016, 8 (49), 33446.
  5. (5) Shirbin, S. J.; Insua, I.; Holden, J. A.; Lenzo, J. C.; Reynolds, E. C.; O'Brien-Simpson, N. M.; Qiao, G. G. Architectural effects of star-shaped “Structurally nanoengineered antimicrobial peptide polymers” (SNAPPs) on their biological activity. Adv. Healthc. Mater. 2018, 7, 1800627.