Proteolytic resistant antimicrobial peptide against pseudomonas aeruginosa keratitis — ASN Events
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  3. Proteolytic resistant antimicrobial peptide against pseudomonas aeruginosa keratitis

Proteolytic resistant antimicrobial peptide against pseudomonas aeruginosa keratitis (#308)

Venkatesh Mayandi 1 2 , Thet Tun Aung 1 2 , Mercy Halleluyah Periayah 1 2 , Eunice Tze Leng Goh 2 , Rajamani Lakshminarayanan 1 2 3
  1. Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Graduate Medical School, Singapore
  2. Singapore Eye Research Institute (SERI), Singapore, SINGAPORE
  3. Department of Pharmacy,, National University of Singapore, Singapore, Singapore.

Aim

Ocular infections, including post-operative complications like infectious endophthalmitis and infectious keratitis, have severe global consequences, leading to morbidity and blindness. Pseudomonas aeruginosa (PA) is largely responsible for debilitating conditions in infectious keratitis. The recent outbreak due to multi-drug resistant (MDR), PA due to contamination of topical eye drops fuel the heightened need for new class of antimicrobial peptides for combating MDR pathogens. The aim of this study is to probe the antimicrobial properties of peptides in tear fluid as well as their hemolytic activity. We determined the in vivo potency of selected peptide in a mice model of PA keratitis.

Methods

Antibacterial activity of linear and branched peptides was compared with the antimicrobial polymer ε-polylysine. MICs and time-kill kinetics assays established their bactericidal activity. Ocular toxicity and antimicrobial activity of selected peptide was evaluated in rabbit model of corneal wound healing and mice model of PA keratitis.

Results

When compared to linear peptides, branched peptides displayed superior antimicrobial properties. εPL and the antimicrobial peptides exhibited potent activity against both ATCC and clinical PA isolates. εPL demonstrated good efficacy with an MIC of 8 μg/ml, complete bacterial eradication within 2 hours at 32 μg/ml (4× MIC). After 21 passages, PA strains did not develop antimicrobial resistance to εPL, whereas significant resistance (512-fold and 1024-fold MIC increase) emerged against Polymyxin B. In vivo, 0.3% w/v εPL in a corneal wound healing rabbit model and topical εPL instillation in a PA keratitis mouse model displayed better sequel than comparator antibiotics.

Conclusion

Pre-clinical murine studies demonstrated εPL (3 mg/ml) effectively reduced PA bioburden (>4 log10 CFU/ml) without hindering corneal epithelial wound healing. This suggests that εPL has the potential to serve as a safe and effective topical antimicrobial agent for treating multidrug resistant P. aeruginosa, with minimal risk of antimicrobial resistance development.

 

 

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