The use of antimicrobial peptides in ophthalmology: an experimental study in corneal preservation and the management of bacterial keratitis.

作者: Mark J Mannis

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摘要: Purpose Bacterial keratitis is an ocular infection with the potential to cause significant visual impairment. Increasing patterns of antibiotic resistance have necessitated development new antimicrobial agents for use in bacterial and other serious infections. With a view exploring novel peptides management infection, we performed series experiments using synthetic designed eradication common ophthalmic pathogens. Methods Experiments were three clinical isolates--Pseudomonas aeruginosa, Staphylococcus aureus, epidermidis--in experimental settings: (1) vitro controlled system 10 mM sodium phosphate buffer, (2) modified chondroitin sulfate-based corneal preservation media (Optisol), (3) vivo animal model (rabbit) simulating keratitis. In all cases, outcomes measured by quantitative microbiological techniques. Results The candidate (CCI A, B, C COL-1) produced total reduction test pathogens buffered saline. Optisol, effective against S epidermidis at temperatures, demonstrated augmented activity 23 degrees gram-positive organisms, but ineffective P aeruginosa. addition EDTA medium killing aeruginosa made no difference organisms. rabbit Pseudomonas keratitis, COL-1 neither nor microbicidal efficacy appeared very narrow dosage range, outside which it be toxic surface. Conclusion Our data indicate that tested not vivo. age increasing resistance, peptides, developed over millions years as innate defense mechanisms plants animals, may topical severe However, modifications drug delivery systems, or both, will necessary application.

参考文章(227)
Francisco J. Garcia-Ferrer, Jay S. Pepose, Patrick R. Murray, Stephen R. Glaser, Jonathan H. Lass, W. Richard Green, Antimicrobial efficacy and corneal endothelial toxicity of DexSol corneal storage medium supplemented with vancomycin. Ophthalmology. ,vol. 98, pp. 863- 869 ,(1991) , 10.1016/S0161-6420(91)32208-5
J.S. Cullor, S. Wood, W. Smith, L. Panico, M.E. Selsted, Bactericidal potency and mechanistic specificity of neutrophil defensins against bovine mastitis pathogens. Veterinary Microbiology. ,vol. 29, pp. 49- 58 ,(1991) , 10.1016/0378-1135(91)90109-S
Stuart B. Levy, Multidrug resistance--a sign of the times. The New England Journal of Medicine. ,vol. 338, pp. 1376- 1378 ,(1998) , 10.1056/NEJM199805073381909
David Andreu, R. B. Merrifield, Haakan Steiner, Hans G. Boman, N-Terminal analogs of cecropin A: synthesis, antibacterial activity, and conformational properties Biochemistry. ,vol. 24, pp. 1683- 1688 ,(1985) , 10.1021/BI00328A017
Regis P. Kowalski, Antifungal Synergism: A Proposed Dosage for Corneal Storage Medium Archives of Ophthalmology. ,vol. 103, pp. 250- 256 ,(1985) , 10.1001/ARCHOPHT.1985.01050020102030
Dan HULTMARK, Ake ENGSTROM, Hans BENNICH, Rashmi KAPUR, Hans G. BOMAN, Insect Immunity: Isolation and Structure of Cecropin D and Four Minor Antibacterial Components from Cecropia Pupae FEBS Journal. ,vol. 127, pp. 207- 217 ,(1982) , 10.1111/J.1432-1033.1982.TB06857.X
Loraine Silvestro, Kushol Gupta, Jeffrey N. Weiser, Paul H. Axelsen, The concentration-dependent membrane activity of cecropin A Biochemistry. ,vol. 36, pp. 11452- 11460 ,(1997) , 10.1021/BI9630826
Katsumi Matsuzaki, Akemi Nakamura, Osamu Murase, Ken-ichi Sugishita, Nobutaka Fujii, Koichiro Miyajima, Modulation of magainin 2-lipid bilayer interactions by peptide charge. Biochemistry. ,vol. 36, pp. 2104- 2111 ,(1997) , 10.1021/BI961870P