Staphylolysin is an effective therapeutic agent for Staphylococcus aureus experimental keratitis

Irina S. Barequet*, Nirit Bourla, Yuval N. Pessach, Mary Safrin, Dalit Yankovich, Dennis E. Ohman, Mordechai Rosner, Efrat Kessler

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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 MSSAinfected 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.

Original languageEnglish
Pages (from-to)223-229
Number of pages7
JournalGraefe's Archive for Clinical and Experimental Ophthalmology
Volume250
Issue number2
DOIs
StatePublished - Feb 2012

Funding

FundersFunder number
Claire and Amedee Maratier Institute of the Tel-Aviv University Sackler Faculty of Medicine
Tel-Aviv University Foundation for Basic Research
Veterans AdministrationI01 BX000477
National Institute of Allergy and Infectious DiseasesR01AI026187
U.S. Public Health Service

    Keywords

    • Antimicrobials
    • Keratitis
    • LasA protease
    • MRSA
    • MSSA
    • Staphylolysin

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