Effect of hybrid peptides of cecropin A and melittin in an experimental model of bacterial keratitis.
Synthetic peptides, ranging from 12 to 18 residues, containing partial sequences from natural cecropin A and melittin were tested for activity in an experimental pseudomonas keratitis model in rabbits. In separate experiments, two Pseudomonas aeruginosa strains: (a) a clinical isolated strain, and (b) an American Type Culture Collection (ATCC) strain, were inoculated into the stroma of one cornea of each rabbit. Peptides were topically applied at 0.1% in phosphate-buffered saline (PBS) and compared with PBS alone and 0.3% gentamicin eye drops. Clinical evaluation, based on the McDonald-Shadduck scale, was performed during a > 48-h period after the bacterial inoculation. The peptide-treated animals showed significantly lower (p < 0.05) inflammatory signs and lower anterior-segment bacterial damage compared with PBS-treated animals, after the first 6 h. The antiinflammatory/antimicrobial activity was non significantly differnt (p > 0.05) from that in animals treated with gentamicin. We conclude that peptides keeping the sequence KWKLFKK from cecropin A and at least the sequence VLKVL from melittin show promise as novel agents in topical ocular therapy of bacterial keratitis.
Nos-Barbera
S
S
Department of Ophthalmology and Visual Sciences, School of Medicine, University of Louisville, KY, USA.
Portoles
M
M
Morilla
A
A
Ubach
J
J
Andreu
D
D
Paterson
C A
CA
D000287:Administration, Topical; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D002851:Chromatography, High Pressure Liquid; D003315:Cornea / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D003320:Corneal Ulcer / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D004195:Disease Models, Animal; D015818:Eye Infections, Bacterial / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D008297:Male; D008555:Melitten / Q000494:pharmacology*; D009883:Ophthalmic Solutions; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D011817:Rabbits; D011897:Random Allocation
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D009883:Ophthalmic Solutions; D010446:Peptide Fragments; D010455:Peptides; D008555:Melitten; C031161:cecropin A