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2004 OMIG, Abstract 5

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LasA Protease as a Therapeutic Agent in Staphylococcal Keratitis
IS Barequet1, Y Pessach2, GJ Ben Simon1, M Safrin1, M Rosner1, E Kessler1. 1Goldschleger Eye Institute, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Hashomer, Israel and 2Department of Ophthalmology, SZMC, Jerusalem, Ben Gurion University of the Negev, Israel

Purpose:To determine the efficacy of LasA protease (LasA), a staphylolytic protease secreted by Pseudomonas aeruginosa, in the management of experimental Staphylococcal keratitis, induced by methicillin-sensitive (MSSA) and methicillin-resistant (MRSA) isolates.
Methods: LasA protease was purified from the culture filtrate of an overexpressing P. aeruginosa strain. Keratitis was induced in New Zealand white rabbits by intrastromal injections of 103 S. aureus cells. Eyes were treated topically with LasA protease or bovine serum albumin (control). Drops were applied every 30 minutes from 4 to 9h post-infection, then hourly for 4 additional hours (early onset), or from 10 to 15h post-infection (late onset). A short regimen (every 30 minutes from 4 to 9h post-infection) was used in studies with 3 additional MRSA strains. Rabbits were sacrificed one hour after cessation of treatment and the corneas were excised and homogenized for bacterial quantification.
Results: In the early-onset therapy group essentially all of the MSSA- and MRSA-infected corneas were sterilized by LasA protease whereas the respective control corneas were heavily infected, with median values of 5xl05 to 4.5xl06 CFU/cornea (P <0.001). In the late-onset therapy group, LasA protease reduced the CFU values in both MSSA and MRSA-infected corneas by 3-4 orders of magnitude as compared to controls (P=0.001). In the short regimen, LasA either sterilized the corneas, or significantly reduced the bacterial proliferation.
Conclusions: LasA protease is effective in treating keratitis caused by methicillin-sensitive or methicillin-resistant S. aureus, supporting its potential use as a new broad-range therapeutic tool for Staphylococcal keratitis.

Disclosure code: N

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