Evaluation of Pseudomonas aeruginosa Staphylolysin (LasA protease) in the Treatment of Experimental Methicillin-Resistant Staphylococcus aureus Endophthalmitis

Abstract

Purpose: : To evaluate the efficacy of staphylolysin (LasA protease), a staphylolytic endopeptidase secreted by Pseudomonas aeruginosa, as a therapy for experimental methicillin-resistant Staphylococcus aureus (MRSA) endophthalmitis.

Methods: : Staphylolysin was purified from the culture filtrate of P. aeruginosa by cation-exchange chromatography. 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 six hours post-infection; (ii) two successive intravitreal injections of staphylolysin given at six and 30 hours post-infection. Control eyes were injected with vehicle alone at the same schedules. The rats were sacrificed 48 hours after infection and the vitreous was withdrawn for determination of colony forming units (CFU).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 one month after intravitreal staphylolysin injection.

Results: : In eyes treated by the single-injection regimen, staphylolysin reduced the mean CFU value per vitreous three fold as compared to control (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 (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.

Keywords: endophthalmitis • enzymes/enzyme inhibitors • injection