Staphylolysin is an effective therapeutic agent for Staphylococcus aureus experimental keratitis

• Published in: Graefe's archive for clinical and experimental ophthalmology Vol. 250; no. 2; pp. 223 - 229
• Main Authors: Barequet, Irina S., Bourla, Nirit, Pessach, Yuval N., Safrin, Mary, Yankovich, Dalit, Ohman, Dennis E., Rosner, Mordechai, Kessler, Efrat
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.02.2012; Springer Nature B.V
• Subjects: Abscesses; Administration, Topical; Animals; Basic Science; Bovine serum albumin; Colony Count, Microbial; Colony-forming cells; Cornea; Cornea - microbiology; Corneal Ulcer - drug therapy; Corneal Ulcer - microbiology; Disease Models, Animal; Drug resistance; Edema; endopeptidase; Endotoxins - administration & dosage; Endotoxins - therapeutic use; Eye Infections, Bacterial - drug therapy; Eye Infections, Bacterial - microbiology; Infection; Inflammation; Keratitis; Medicine; Medicine & Public Health; Methicillin-Resistant Staphylococcus aureus - physiology; Ophthalmology; Pseudomonas aeruginosa; Rabbits; Staphylococcal Infections - drug therapy; Staphylococcal Infections - microbiology; Staphylococcus aureus; Treatment Outcome; MSSA; LasA protease; Keratitis; Staphylolysin; Antimicrobials; MRSA
• ISSN: 0721-832X; 1435-702X
• DOI: 10.1007/s00417-011-1822-6

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 10 3 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.