Evaluation of Pseudomonas aeruginosa staphylolysin (LasA protease) in the treatment of methicillin-resistant Staphylococcus aureus endophthalmitis in a rat model.
BACKGROUND
Therapy of S. aureus ocular infections is increasingly challenging due to emerging resistant strains. Staphylolysin (also called LasA protease) is a staphylolytic endopeptidase secreted by Pseudomonas aeruginosa. The purpose of this study was to evaluate the efficacy of staphylolysin as a therapy for experimental methicillin-resistant Staphylococcus aureus (MRSA) endophthalmitis, focusing on its bactericidal activity.


METHODS
Endophthalmitis was induced in the right eyes of 46 rats by an intravitreal injection of 50-160 MRSA cells. Two therapeutic regimens were evaluated: (i) an intravitreal injection of staphylolysin at 6 hours post-infection; (ii) two successive intravitreal injections of staphylolysin given at 6 and 30 hours post-infection. Control eyes were injected with vehicle alone at the same times. The rats were sacrificed 48 hours after infection, and the vitreous was withdrawn for determination of colony forming units (CFU). Potential adverse effects of intravitreal staphylolysin injection were assessed histopathologically in four uninfected eyes, enucleated from rats sacrificed 1 month after intravitreal staphylolysin injection.


RESULTS
In eyes treated by the single-injection regimen, staphylolysin reduced the mean CFU value per vitreous threefold as compared to control (2,055 +/- 3,144 and 6,432 +/- 6,389 CFU/vitreous, respectively; P = 0.02). The repeated injection protocol was more effective, reducing the mean CFU value per vitreous by two orders of magnitude as compared to control (1,148 +/- 3,096 and 143,519 +/- 151,358 CFU/vitreous, respectively; P = 0.0005). Histopathological analysis showed no structural damage in eyes injected intravitreally with staphylolysin.


CONCLUSIONS
Staphylolysin is effective in the treatment of experimental MRSA-induced endophthalmitis in rats, and causes no morphological adverse effects to ocular tissues. Staphylolysin may be beneficial in the treatment of S. aureus endophthalmitis in humans.
Barequet
Irina S
IS
Maurice and Gabriela Goldschleger Eye Research Institute, Sackler Faculty of Medicine, Tel Aviv University, Sheba Medical Center, Tel Hashomer, Israel. ibarequet@hotmail.com
Habot-Wilner
Zohar
Z
Mann
Oran
O
Safrin
Mary
M
Ohman
Dennis E
DE
Kessler
Efrat
E
Rosner
Mordechai
M
D000818:Animals; D015169:Colony Count, Microbial; D004334:Drug Administration Schedule; D009877:Endophthalmitis / Q000382:microbiology*; D004731:Endotoxins / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use*; D007267:Injections; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D013203:Staphylococcal Infections / Q000188:drug therapy*; D016896:Treatment Outcome; D014822:Vitreous Body / Q000382:microbiology
D004731:Endotoxins; C016110:staphylolysin