June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Cationic Branched Peptides as Antibiotic Adjuvants
Author Affiliations & Notes
  • Rajamani Lakshminarayanan
    Ocular Proteomics and Anti-Infectives, Singapore Eye Research Institute, Singapore, Singapore
    SRP in Neuroscience and Behavioral Disorders, Duke-NUS Graduate School of Medicine, Singapore, Singapore
  • Eunice Goh Tze Leng
    Ocular Proteomics and Anti-Infectives, Singapore Eye Research Institute, Singapore, Singapore
  • Liu Shouping
    Ocular Proteomics and Anti-Infectives, Singapore Eye Research Institute, Singapore, Singapore
    SRP in Neuroscience and Behavioral Disorders, Duke-NUS Graduate School of Medicine, Singapore, Singapore
  • Roger Beuerman
    Ocular Proteomics and Anti-Infectives, Singapore Eye Research Institute, Singapore, Singapore
    SRP in Neuroscience and Behavioral Disorders, Duke-NUS Graduate School of Medicine, Singapore, Singapore
  • Footnotes
    Commercial Relationships Rajamani Lakshminarayanan, None; Eunice Goh Tze Leng, None; Liu Shouping, None; Roger Beuerman, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 2466. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Rajamani Lakshminarayanan, Eunice Goh Tze Leng, Liu Shouping, Roger Beuerman; Cationic Branched Peptides as Antibiotic Adjuvants. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2466.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose: The purpose of this study is to investigate the efficacy of a series of branched peptides in increasing the potency of aminoglycosides and fluorquinolones against multi-drug resistant Gram-negative pathogens.

Methods: The outer membrane (OM) permeability and affinity for lipopolysaccharides (LPS) were determined by N-1-phenyl naphthylamine, Bodipy-TR cadevarine assays and isothermal titration calorimetry. The fractional inhibitory concentration index (FICI) was determined by checker board assay. Finally, the antibiotic adjuvant capacity of the most efficacious peptides was determined by bacterial viability assays.

Results: Branched peptides carrying two copies of the putative sequence RGRKX1X2X3X4 or RGX1X2X3X4RR, where X1-X4 are natural or unnatural amino acid residues were synthesized and their antimicrobial properties and their ability to permeabilize the OM of P. aeruginosa were determined. When compared to the parent peptide B2088, the newly designed peptides displayed weak antimicrobial properties but superior ability to potentiate the antimicrobial activities of chloramphenicol, aminoglycosides (gentamycin and tobramycin) and fluoroquinolones (moxifloxacins and levofloxacin) as confirmed by checker board assays. To determine the efficacy, bacterial viability was determined for antibiotic eye drop solutions (Tobrex and gentamycin) in 10-fold serial dilutions with or without the adjuvants. Addition of mM concentrations of the peptides to 10-5 × diluted commercially available antibiotics solutions caused >3 log10 decrease in bacterial viability when compared to antibiotics alone. These results suggest that the peptides potentiate the antimicrobial efficacy of antibiotic eye drops as well.

Conclusions: The results showed that cationic branched peptides which lacks potent antimicrobial activity can be used as adjuvants that can potentiate the antimicrobial efficacies of commercial eye drop medications.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×