Abstract
Abstract: :
Purpose: To investigate the corneal virulence of toxin–deficient mutants of S. aureus in young and aged mice using a topical inoculation model of keratitis. Methods:Corneas of young (6–7 weeks of age) and aged (9–12 months of age) A/J mice were scarified and topically inoculated with log phase S. aureus parent strain (8325–4), an alpha–toxin deficient mutant (DU1090), or an Agr–defective mutant (ISP546). At various times postinfection (PI), mice underwent slit lamp examination (SLE) and eyes were analyzed for histopathological changes. Whole eye homogenates were cultured in triplicate for bacterial colony forming units (CFU) and assayed for myeloperoxidase (MPO) activity. Results:Whereas young A/J mice infected with the parent strain demonstrated gross pathologic signs of infection and significant increases in SLE scores from 5 to 9 days PI, young mice infected with either mutant strain demonstrated less severe signs of infection at these time points (P = 0.0001). Histopathology performed at 9 days PI in young mice confirmed the pathological differences between infections with the parent versus mutant strains of S. aureus. In aged mice, infection with the parent strain caused such severe pathology that infections had to be terminated by day 3 PI. In contrast, for aged mice infected with either mutant strain of S. aureus, the SLE scores at 1 to 3 days PI were significantly less than that of aged mice infected with the parent strain (P ≤ 0.025). Infections of aged mice with the mutant strains caused limited to moderate pathology, even through day 9 PI, as evidenced by the SLE scores and findings of histopathological analysis. Bacterial loads and MPO activities for both young and aged mice were maximal at day 1 PI and similar overall for all bacterial strains throughout infection. Conclusions: Bacterial toxins, and specifically alpha–toxin, mediate corneal pathology in mice. Differences in severity of S. aureus keratitis in young versus aged mice could relate to the toxin susceptibility of the infected eye.
Keywords: Staphylococcus • keratitis • aging