title: Activity of a melimine derived peptide Mel4 against Stenotrophomonas, Delftia, Elizabethkingia, Burkholderia and biocompatibility as a contact lens coating.
abstract: OBJECTIVE
  To determine the antimicrobial activity of the melimine derived peptide Mel4 against Delftia, Stenotrophomonas, Elizabethkingia, Burkholderia and to investigate biocompatibility of Mel4 as an antimicrobial coating on contact lenses in animals and humans.
  
  
  METHODS
  In vitro antimicrobial activity of Mel4 was determined against the four Gram negative bacteria by investigating growth curves for 24h followed by viable counts to determine the minimum inhibitory concentration (MIC). Contact lenses were coated by covalently binding Mel4, characterized by amino acid analysis, and were investigated for changes in lens parameters. Safety of Mel-4 coated lenses were determined in a rabbit model of daily contralateral wear. A prospective, randomised, double-masked, contralateral, 1week daily wear human clinical trial was used to evaluate subjective responses and ocular physiology.
  
  
  RESULTS
  Mel4 was active against all the bacteria tested (MIC50ranged from 31-1000μgml-1) and produced an antimicrobial surface on contact lenses. Mel4-coating resulted hydrophilic surface without any significant change in contact lens parameters, and showed no signs of cytotoxicity or ocular irritation during rabbit wear. During human clinical trial, there were no differences between Mel4 coated and uncoated contact lenses in lens performance indicators and ocular signs such as corneal fluorescein staining. Mel4 and control uncoated lenses had no differences in ocular symptoms during lens wear.
  
  
  CONCLUSIONS
  Mel4 has achieved antimicrobial activity against variety of Gram negative bacteria that are often resistant to the action of cationic peptides and have been implicated in contact lens related adverse events. Mel4-coated contact lenses were safe to wear.
authors.affiliation: School of Optometry and Vision Science, University of New South Wales, Australia. Electronic address: debarun.dutta@unsw.edu.au.
authors.forename: Debarun
authors.initials: D
authors.lastname: Dutta
authors.affiliation: School of Optometry and Vision Science, University of New South Wales, Australia.
authors.forename: Timothy
authors.initials: T
authors.lastname: Zhao
authors.affiliation: School of Optometry and Vision Science, University of New South Wales, Australia.
authors.forename: Kai Bing
authors.initials: KB
authors.lastname: Cheah
authors.affiliation: Department of Biology, University of Copenhagen, Denmark.
authors.forename: Larke
authors.initials: L
authors.lastname: Holmlund
authors.affiliation: School of Optometry and Vision Science, University of New South Wales, Australia.
authors.forename: Mark D P
authors.initials: MDP
authors.lastname: Willcox
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D001422:Bacterial Adhesion / Q000187:drug effects; D019117:Burkholderia / Q000187:drug effects* / Q000302:isolation & purification; D019121:Burkholderia Infections / Q000382:microbiology / Q000517:prevention & control*; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D003261:Contact Lenses / Q000382:microbiology*; D004195:Disease Models, Animal; D004866:Equipment Contamination / Q000517:prevention & control; D015818:Eye Infections, Bacterial / Q000382:microbiology / Q000517:prevention & control*; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000382:microbiology / Q000517:prevention & control; D008422:Materials Testing / Q000379:methods; D008826:Microbial Sensitivity Tests / Q000379:methods; D011446:Prospective Studies; D011817:Rabbits; D020588:Stenotrophomonas / Q000187:drug effects* / Q000302:isolation & purification
chemical_list: D023181:Antimicrobial Cationic Peptides; D020099:Coated Materials, Biocompatible; C541912:melimine
keywords: Antimicrobial; Contact lens; Delftia; Mel4; Melimine; Stenotrophomonas