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Effects of Toxin Production in a Murine Model of Staphylococcus aureus Keratitis

¹From the Departments of Microbiology, Immunology, and Parasitology, and ²Pathology, Louisiana State University Health Sciences Center, New Orleans, Louisiana; and the ³Department of Ophthalmology, LSU Eye Center, New Orleans, Louisiana.

PURPOSE. To investigate the corneal virulence of toxin-deficient mutants of Staphylococcus aureus in young and aged mice in a topical inoculation model of keratitis.

METHODS. Corneas of young and aged A/J mice were scarified and topically inoculated with a log phase S. aureus parent strain (8325-4), an -toxin-deficient mutant (DU1090), or an Agr-defective mutant (ISP546) deficient in production of multiple toxins or with purified -toxin. Slit lamp examination (SLE) and histopathology were performed, and bacterial colony-forming units (CFU) and myeloperoxidase (MPO) activity were determined.

RESULTS. The infection of young mice with the mutant strains demonstrated significantly lower SLE scores (P 0.0001) and reduced histopathologic changes compared with infections with the parent bacterial strain. Either mutant strain of S. aureus produced SLE scores in aged mice through 9 days after infection (PI) that were significantly lower than those of aged mice similarly infected with the toxin-producing parent strain (P 0.0001). Despite use of identical inocula, the CFU per eye were greater for the parent than the mutant strains from 1 to 5 days PI in the young mice (P 0.0372) and from 1 to 3 days PI in the aged mice (P 0.0018). MPO activities were at the maximum at day 1 PI and were similar overall for all infections. Administration of purified -toxin caused greater gross and histopathologic changes in eyes of aged mice than in those of young mice.

CONCLUSIONS. Bacterial toxins, and especially -toxin, can mediate corneal disease in mice. Differences in severity of S. aureus keratitis in aged versus young mice correlates with their susceptibility to -toxin.

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