Poster Presentation 15th Lorne Infection and Immunity 2025

Evaluation of antimicrobial and antibiofilm properties of novel synthetic antimicrobial peptides (#337)

Suzana Krkic 1 , Pradip Sedhai 1 , Elena Pirogova 2 , Taghrid Istivan 1
  1. School of Science, Biosciences, RMIT University, Bundoora, VIC, Australia
  2. School of Engineering, Biomedical Engineering , RMIT University, Melbourne, VIC, Australia

Antimicrobial resistance is a critical global health concern, necessitating the development of new alternative therapeutic strategies. Antimicrobial peptides (AMPs), and innate immune effector molecules, represent a promising avenue due to their broad-spectrum antimicrobial activity and the potential application as alternatives to conventional antibiotics. In this study, synthetic AMPs, designed using the Resonant Recognition Model (RRM) [1,2] as analogues to mammalian antimicrobial molecules, were assessed for their antimicrobial efficacy against the Gram-positive bacterium Staphylococcus aureus ATCC 25923, the methicillin-resistant S. aureus (MRSA) strain 344/2-24, and the Gram-negative bacterium Pseudomonas aeruginosa ATCC 27853. The antimicrobial effect of small molecular weight analogues to Azurocidin, a natural human antimicrobial peptide, was assessed using RRM-Az18 (18 mer) and RRM-Az35 (35 mer) as the bioactive molecules, in addition to RRM-AzC, a negative control peptide designed by the same model.  Furthermore, the antibiofilm effect of these AMPs and their ability to inhibit the biofilm formation of P. aeruginosa ATCC 27853 was assessed. Both RRM-Az18 and RRM-Az35 demonstrated a significant antimicrobial activity against S. aureus 25923 and MRSA 244/2-24, with RRM-Az35 also showing efficacy against planktonic P. aeruginosa 27853. However, neither peptide exhibited substantial activity against the biofilm of P. aeruginosa. Yet, other bioactive RRM-designed peptides which are analogues to known therapeutic natural proteins [3,4] were evaluated for their antimicrobial activity and found to be more efficient in controlling the biofilm formation of P. aeruginosa and other Gram-negative bacterial pathogens. This study underscores the application of the RRM to design small molecular weight peptides possessing the desired antimicrobial therapeutic function, and the potential development of these novel AMPs as effective agents to defy antimicrobial resistance towards current chemotherapeutics.

  1. Cosic I (1997) The Resonant recognition model of macromolecular bioactivity: theory and applications. In Meier T, Saluz HP, editors. Biomethods. Basel: Birkhauser Verlag: Vol 9.
  2. Hu J, Peidaee P, Elshagmani E, Istivan T, Pirogova E (2013). The effects of synthetic azurocidin peptide analogue on Staphylococcus aureus bacterium. Proc. of 13th IEEE Int. Conf. on Bioinformatics and Bioengineering, Greece, Nov. 2013.
  3. Pirogova E, Istivan T, Gan E, Cosic I (2011) Advances in methods for therapeutic peptide discovery, design and development. Curr Pharma Biotech, Vol.12:1117–1127.
  4. Istivan T, Pirogova E., et al. (2011) Biological effects of a denovo designed myxoma virus peptide analogue: evaluation of cytotoxicity on tumor cells. PlosOne, Vol. 6(9), 1-10.