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 10(6) (MSSA) and 5 x 10(5) (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 10(6) and 5 x 10(5) 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.