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 alpha-toxin-deficient mutant (DU1090), or an Agr-defective mutant (ISP546) deficient in production of multiple toxins or with purified alpha-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 < or = 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 < or = 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 < or = 0.0372) and from 1 to 3 days PI in the aged mice (P < or = 0.0018). MPO activities were at the maximum at day 1 PI and were similar overall for all infections. Administration of purified alpha-toxin caused greater gross and histopathologic changes in eyes of aged mice than in those of young mice. CONCLUSIONS: Bacterial toxins, and especially alpha-toxin, can mediate corneal disease in mice. Differences in severity of S. aureus keratitis in aged versus young mice correlates with their susceptibility to alpha-toxin.
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 alpha-toxin-deficient mutant (DU1090), or an Agr-defective mutant (ISP546) deficient in production of multiple toxins or with purified alpha-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 < or = 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 < or = 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 < or = 0.0372) and from 1 to 3 days PI in the aged mice (P < or = 0.0018). MPO activities were at the maximum at day 1 PI and were similar overall for all infections. Administration of purified alpha-toxin caused greater gross and histopathologic changes in eyes of aged mice than in those of young mice. CONCLUSIONS: Bacterial toxins, and especially alpha-toxin, can mediate corneal disease in mice. Differences in severity of S. aureus keratitis in aged versus young mice correlates with their susceptibility to alpha-toxin.
Authors: Robert M Q Shanks; Nicholas A Stella; Kristin M Hunt; Kimberly M Brothers; Liang Zhang; Patrick H Thibodeau Journal: Infect Immun Date: 2015-05-04 Impact factor: 3.441
Authors: Victor E Reviglio; Andres Grenat; Federico Pegoraro; Ruben H Sambuelli; Tayyib Rana; Irene C Kuo Journal: J Ophthalmol Date: 2009-10-15 Impact factor: 1.909
Authors: Quincy C Moore; Clare C McCormick; Erin W Norcross; Chinwendu Onwubiko; Melissa E Sanders; Jonathan Fratkin; Larry S McDaniel; Richard J O'Callaghan; Mary E Marquart Journal: Ophthalmic Res Date: 2009-07-23 Impact factor: 2.892