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Antimicrobial Agents and Chemotherapy, May 2004, p. 1681-1687, Vol. 48, No. 5
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.5.1681-1687.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Pseudomonas aeruginosa LasA Protease in Treatment of Experimental Staphylococcal Keratitis

Maurice and Gabriela Goldschleger Eye Research Institute, Sheba Medical Center, Tel Aviv University Sackler Faculty of Medicine, Tel-Hashomer 52621, Israel,¹ Medical College of Virginia Campus of Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, Virginia 23298-0678²

Received 15 July 2003/ Returned for modification 30 November 2003/ Accepted 19 January 2004

LasA protease is a staphylolytic endopeptidase secreted by Pseudomonas aeruginosa. We have examined the effectiveness of LasA protease in the treatment of staphylococcal keratitis caused by methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) isolates in a rabbit model. Keratitis was induced by intrastromal injection of the bacteria. The eyes were treated topically, and the efficacy of LasA protease was compared to those of lysostaphin (a staphylolytic protease secreted by Staphylococcus simulans) and vancomycin. When treatment was initiated early (4 h) after infection, practically all of the MSSA- and MRSA-infected corneas were sterilized by LasA protease, and its efficacy in eradicating the bacteria was comparable to those of lysostaphin and vancomycin. By contrast, most of the control corneas were heavily infected, with median values of 4.5 x 10⁶ (MSSA) and 5 x 10⁵ (MRSA) CFU/cornea (P < 0.001). When treatment was initiated late (10 h) after infection, LasA protease reduced the numbers of CFU in both MSSA- and MRSA-infected corneas by 3 to 4 orders of magnitude compared to the numbers of CFU for the controls (median values, 1,380 and 30 CFU/cornea, respectively, for the treated animals compared to 1.2 x 10⁶ and 5 x 10⁵ CFU/cornea for the respective controls [P = 0.001]), and it was more effective than vancomycin in eradicating MRSA cells (P = 0.02). In both the early- and the late-treatment protocols, the clinical scores for eyes treated with LasA protease were significantly lower than those for the eyes of the corresponding controls and comparable to those for the lysostaphin- and vancomycin-treated eyes. We conclude that LasA protease is effective in the treatment of experimental S. aureus keratitis in rabbits and may have potential for the treatment of disease in humans.

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