Pseudomonas aeruginosa LasA protease in treatment of experimental staphylococcal keratitis.
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.
Barequet
Irina S
IS
Maurice and Gabriela Goldschleger Eye Research Institute, Sheba Medical Center, Tel Aviv University Sackler Faculty of Medicine, Tel-Hashomer 52621, Israel.
Ben Simon
Guy J
GJ
Safrin
Mary
M
Ohman
Dennis E
DE
Kessler
Efrat
E
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D001426:Bacterial Proteins; D015169:Colony Count, Microbial; D003315:Cornea / Q000382:microbiology; D006801:Humans; D007634:Keratitis / Q000188:drug therapy* / Q000382:microbiology; D008248:Lysostaphin / Q000494:pharmacology / Q000627:therapeutic use; D008666:Metalloendopeptidases / Q000627:therapeutic use*; D008712:Methicillin / Q000494:pharmacology; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D010406:Penicillins / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000201:enzymology*; D011817:Rabbits; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects; D014640:Vancomycin / Q000494:pharmacology / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D010406:Penicillins; D014640:Vancomycin; D008666:Metalloendopeptidases; D008248:Lysostaphin; C066371:staphylolytic protease; D008712:Methicillin