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2004
OMIG, Abstract 5
OMIG
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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
OMIG
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