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Evaluation of Pseudomonas aeruginosa staphylolysin (LasA protease) in the treatment of methicillin-resistant Staphylococcus aureus endophthalmitis in a rat model

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Abstract

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 The rats were sacrificed 48 hours after infection, and the vitreous was withdrawn for determination of colony forming units (CFU).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.

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Acknowledgements

Supported by grants from the Maratier Foundation for the study of Blindness and Visual Disorders of the Tel Aviv University Sackler Faculty of Medicine (ISB and EK), the Tel Aviv University Foundation for Basic Research (EK), Public Health Service grant AI 26187 from the National Institute of Allergy and Infectious Diseases (DEO) and in part by Veterans Administration Medical Research Funds (DEO).

The authors thank Prof. David Steinberg for assistance with statistical analyses and Dr. Nathan Keller for providing the MRSA strain.

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Authors and Affiliations

  1. Maurice and Gabriela Goldschleger Eye Research Institute, Sackler Faculty of Medicine, Tel Aviv University, Sheba Medical Center, Tel Hashomer, Israel

    Irina S. Barequet, Zohar Habot-Wilner, Mary Safrin, Efrat Kessler & Mordechai Rosner

  2. Department of Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

    Oran Mann

  3. Department of Microbiology and Immunology, Virginia Commonwealth University and Veterans Affairs Medical Centers, Richmond, VA, 23298, USA

    Dennis E. Ohman

  4. Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer, 52621, Israel

    Irina S. Barequet

Authors
  1. Irina S. Barequet
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  2. Zohar Habot-Wilner
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  3. Oran Mann
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  4. Mary Safrin
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  5. Dennis E. Ohman
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  6. Efrat Kessler
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  7. Mordechai Rosner
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Corresponding author

Correspondence to Irina S. Barequet.

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The authors have no proprietary interest in any aspect of this study.

The authors have full control of all primary data, and they agree to allow Graefe's Archive for Clinical and Experimental Ophthalmology to review their data upon request.

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Barequet, I.S., Habot-Wilner, Z., Mann, O. et al. Evaluation of Pseudomonas aeruginosa staphylolysin (LasA protease) in the treatment of methicillin-resistant Staphylococcus aureus endophthalmitis in a rat model. Graefes Arch Clin Exp Ophthalmol 247, 913–917 (2009). https://doi.org/10.1007/s00417-009-1061-2

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  • DOI: https://doi.org/10.1007/s00417-009-1061-2

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