CliniCon Oral Presentation Australian Society for Microbiology Annual Scientific Meeting 2023

The ability of covalently bound peptoids to reduce adhesion of Pseudomonas aeruginosa to contact lenses  (93255)

Manjulatha Sara 1 , Rajesh Kuppusamy 1 , Alex Hui 1 , Edgar Wong 1 , Naresh Kumar 1 , Annelise Barron 2 , Mark Willcox 1
  1. University of New South Wales, Kingsford, NEW SOUTH WALES, Australia
  2. Department of Bioengineering, Stanford school of medicine, Stanford University , , California, United state of America

Purpose: A cationic peptide, Mel4, bound to contact lenses has completed a phase III clinical trial and had the ability to prevent >60% of infiltrative events (1). However, the lenses lost their activity after six nights of wear, probably due to digestion of Mel4 by tear enzymes (2). Peptoids based upon N-substituted glycine as a backbone are protease-resistant (3). This study evaluated the activity of peptoids covalently immobilized on etafilcon A contact lenses to inhibit binding of Pseudomonas aeruginosa. 

Methods: The minimum inhibitory concentration (MIC) of  antimicrobial peptide and peptoids were determined by microbroth dilution method against P. aeruginosa 6294, polymyxin-resistant P. aeruginosa 123, and beta-lactamase resistant ATCC 19660. The cationic peptide melimine and peptoids TM5 and TM18 were covalently bound to etafilcon A via the EDC chemical reaction (4). Bacterial adhesion was performed by adding 5x106 CFU mL-1 of each strain to contact lenses and incubating for 18 hours at 37°C. The toxicity of the compounds was measured by exposing coated contact lenses to human corneal epithelial cells. 

Results: The MIC of compounds TM5 and TM18 against three strains of P. aeruginosa were 18-37 µM and 12-25 µM, respectively. The adhesion of all strains of P. aeruginosa to lenses was 5.6±0.21 CFU mL-1 cells/lens. Bound melimine resulted in 3.1±0.07 log10  reduction in bacterial adhesion. TM5-bound lenses were non-toxic, and TM18-bound lenses produced 30% toxicity to corneal epithelial cells. 

Conclusion: The peptoids TM5 and TM18 both had potent activity against multidrug-resistant  strains of P. aeruginosa, retained their activity when covalently bound to etafilcon A lenses, and TM5 showed no toxicity, while TM18 showed 30% toxicity to corneal epithelial cells. This indicates that the peptoid TM5 may be an excellent alternative for potential development within antimicrobial lenses. 

   

  1. 1. Kalaiselvan, P., et al., Effect of antimicrobial contact lenses on corneal infiltrative events: A randomized clinical trial. Translational Vision Science & Technology, 2021. 10(7): p. 32-32. 2. Kalaiselvan, P., et al., The time-course of retention of anti-adhesion activity of Mel-4 peptide coated contact lenses. Investigative Ophthalmology & Visual Science, 2018. 59(9): p. 1766-1766. 3. Chongsiriwatana, N.P., et al., Short alkylated peptoid mimics of antimicrobial lipopeptides. Antimicrob Agents Chemother, 2011. 55(1): p. 417-20. 4. Dutta, D., N. Kumar, and M. D. P. Willcox, Antimicrobial activity of four cationic peptides immobilised to poly-hydroxyethylmethacrylate. Biofouling, 2016. 32(4): p. 429-438.