Abstract
Many of the virulence factors that have been characterized for group A streptococci (GAS) are not expressed in all clinical isolates. One putative virulence factor that is present among most is streptolysin O (Slo), a protein with well-characterized cytolytic activity for many eukaryotic cells types. In other bacterial pathogens, proteins homologous to Slo have been shown to be essential for virulence, but the role of Slo in GAS had not been previously examined. To investigate the role of Slo in GAS virulence, we examined both revertible and stable slo mutants in a mouse model of invasive disease. When the revertible slo mutant was used to infect mice, the reversion frequency of bacteria isolated from the wounds and spleens of infected animals was more than 100 times that of the inoculum, indicating that there was selective pressure in the animal for Slo(+) GAS. Experiments with the stable slo mutant demonstrated that Slo was not necessary for the formation of necrotic lesions, nor was it necessary for escape from the lesion to cause disseminated infection. Bacteria were present in the spleens of 50% of the mice that survived infection with the stable slo mutant, indicating that dissemination of Slo(-) GAS does not always cause disease. Finally, mice infected with the stable slo mutant exhibited a significant decrease in mortality rates compared to mice infected with wild-type GAS (P < 0.05), indicating that Slo plays an important role in GAS virulence.