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Dalia O. Girgis, Gregory D. Sloop, Julian M. Reed, Richard J. O’Callaghan; Effects of Toxin Production in a Murine Model of Staphylococcus aureus Keratitis. Invest. Ophthalmol. Vis. Sci. 2005;46(6):2064-2070. doi: 10.1167/iovs.04-0897.
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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 α-toxin-deficient mutant (DU1090), or an Agr-defective mutant (ISP546) deficient in production of multiple toxins or with purified α-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 α-toxin caused greater gross and histopathologic changes in eyes of aged mice than in those of young mice.
conclusions. Bacterial toxins, and especially α-toxin, can mediate corneal disease in mice. Differences in severity of S. aureus keratitis in aged versus young mice correlates with their susceptibility to α-toxin.
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