title: Corneal virulence of Staphylococcus aureus: roles of alpha-toxin and protein A in pathogenesis.
abstract: Staphylococcus aureus produces a variety of proteins, including alpha-toxin and protein A, that could contribute to corneal tissue damage during keratitis. We examined corneal infections produced by intrastromal injection of four S. aureus strains--three isogenic mutants, one lacking alpha-toxin (Hly- Spa+), one lacking protein A (Hly+ Spa-), and one lacking both alpha-toxin and protein A (Hly- Spa-), and the wild type (Hly+ Spa+)--in a rabbit model of experimental keratitis. Rabbit corneas were injected intrastromally with 100 CFU of one of the four strains, and the eyes were examined by slit lamp biomicroscopy over a 25-h period. Corneal homogenates were used for determination of CFU and neutrophil myeloperoxidase activity at 5-h intervals. All strains had the same logarithmic growth curve from 0 to 10 h postinfection, after which CFU remained constant at 10(7) CFU per cornea. By 15 h postinfection, slit lamp examination scores were significantly higher for eyes infected with Hly+ strains than for Hly(-)-infected eyes. At this time, distinct epithelial erosions were seen in Hly(+)-infected eyes but not in Hly(-)-infected eyes. Myeloperoxidase activity was significantly greater for Hly(+)-infected corneas than for Hly(-)-infected corneas at both 20 and 25 h postinfection. Spa(+)- and Spa(-)-infected eyes showed no differences in slit lamp examination scores or myeloperoxidase activities. These results suggest that alpha-toxin, but not protein A, is a major virulence factor in staphylococcal keratitis, mediating the destruction of corneal tissue in eyes infected with this bacterial pathogen.
authors.affiliation: Department of Microbiology, Immunology and Parasitology, Louisiana State University Medical Center, New Orleans 70112.
authors.forename: M C
authors.initials: MC
authors.lastname: Callegan
authors.forename: L S
authors.initials: LS
authors.lastname: Engel
authors.forename: J M
authors.initials: JM
authors.lastname: Hill
authors.forename: R J
authors.initials: RJ
authors.lastname: O'Callaghan
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000633:toxicity*; D005098:Exotoxins / Q000633:toxicity*; D006460:Hemolysin Proteins / Q000633:toxicity*; D007634:Keratitis / Q000209:etiology*; D011817:Rabbits; D013205:Staphylococcal Protein A / Q000633:toxicity*; D013211:Staphylococcus aureus / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D001427:Bacterial Toxins; D005098:Exotoxins; D006460:Hemolysin Proteins; D013205:Staphylococcal Protein A; C021091:staphylococcal alpha-toxin