Effects of toxin production in a murine model of Staphylococcus aureus keratitis.
OBJECTIVE
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.
Girgis
Dalia O
DO
Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, 70112, USA.
Sloop
Gregory D
GD
Reed
Julian M
JM
O'Callaghan
Richard J
RJ
D000375:Aging; D000818:Animals; D001427:Bacterial Toxins; D015169:Colony Count, Microbial; D003315:Cornea / Q000382:microbiology* / Q000473:pathology; D004195:Disease Models, Animal; D015818:Eye Infections, Bacterial / Q000382:microbiology* / Q000473:pathology; D006460:Hemolysin Proteins / Q000502:physiology*; D007634:Keratitis / Q000382:microbiology* / Q000473:pathology; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D009195:Peroxidase / Q000378:metabolism; D013203:Staphylococcal Infections / Q000382:microbiology* / Q000473:pathology; D013211:Staphylococcus aureus / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D014774:Virulence
D001427:Bacterial Toxins; D006460:Hemolysin Proteins; C021091:staphylococcal alpha-toxin; D009195:Peroxidase