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Staphylolysin is an effective therapeutic agent for Staphylococcus aureus experimental keratitis

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Abstract

Background

Therapy of S. aureus keratitis is increasingly challenging due to emerging resistant strains. Staphylolysin (LasA protease) is a staphylolytic endopeptidase secreted by Pseudomonas aeruginosa. The purpose of the current study was to study the effect of treatment with staphylolysin on experimental keratitis caused by various Staphylococcus aureus strains.

Methods

The therapeutic effect was studied in a keratitis model induced in rabbits by intrastromal injections of 103 S. aureus cells of three different methicillin-resistant S. aureus (MRSA) strains and one methicillin-susceptible S. aureus strain (MSSA). Topical treatment with either staphylolysin or bovine serum albumin (BSA; control) was applied every half hour for 5 h, starting at 4 h after infection. Corneas were removed for bacterial quantification. Histopathological analysis was performed on MSSA-infected rabbits, killed at either one or 84 h after completion of treatment and on uninfected eyes 1 h after treatment termination.

Results

The number of bacteria in the staphylolysin-treated corneas was significantly reduced in all infections with the four S. aureus strains studied as compared to controls: the staphylolysin-treated eyes infected with MRSA strains were either completely sterilized or showed a 3–4 orders of magnitude decrease in the number of cfu/cornea (p = 0.004 to 0.005); all of the staphylolysin-treated MSSA-infected eyes were sterile. Histopathological analysis of the methicillin-sensitive (MSSA) strain-infected eyes at 84 h after completion of treatment showed moderate inflammation in the staphylolysin-treated eyes as compared with extensive abscess formation in the control group. The uninfected corneas showed only mild stromal edema in both the staphylolysin and BSA-treated groups.

Conclusions

Staphylolysin provided long-lasting protection against several strains of S. aureus, evident by both its strong anti-bacterial activity and beneficial histopathological results of treatment.

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Acknowledgments

This study was supported by the Claire and Amedee Maratier Institute of the Tel-Aviv University Sackler Faculty of Medicine (to I.S.B., M.R., and E.K), the Tel-Aviv University Foundation for Basic Research (to E.K.), Public Health Service grant AI 26187 from the National Institute of Allergy and Infectious Diseases (to D.E.O.), and in part, by Veterans Administration Medical Research Grant I01 BX000477 (to D.E.O.). The authors have full control of all primary data and agree to allow Graefe's Archive for Clinical and Experimental Ophthalmology to review the data upon request.

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Authors and Affiliations

  1. Maurice and Gabriela Goldschleger Eye Research Institute, Tel Aviv University Sackler Faculty of Medicine, Sheba Medical Center, Tel-Hashomer, 52621, Israel

    Irina S. Barequet, Nirit Bourla, Mary Safrin, Dalit Yankovich, Mordechai Rosner & Efrat Kessler

  2. Department of Ophthalmology, SZMC, Jerusalem, Ben Gurion University of the Negev, Negev, Israel

    Yuval N. Pessach

  3. Virginia Commonwealth University Medical Center and McGuire Veterans Affairs Medical Center, Richmond, VA, 23298-0678, USA

    Dennis E. Ohman

Authors
  1. Irina S. Barequet
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  2. Nirit Bourla
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  3. Yuval N. Pessach
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  4. Mary Safrin
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  5. Dalit Yankovich
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  6. Dennis E. Ohman
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  7. Mordechai Rosner
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  8. Efrat Kessler
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Correspondence to Irina S. Barequet.

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Barequet, I.S., Bourla, N., Pessach, Y.N. et al. Staphylolysin is an effective therapeutic agent for Staphylococcus aureus experimental keratitis. Graefes Arch Clin Exp Ophthalmol 250, 223–229 (2012). https://doi.org/10.1007/s00417-011-1822-6

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  • DOI: https://doi.org/10.1007/s00417-011-1822-6

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