Role of Streptolysin O in a Mouse Model of Invasive Group A Streptococcal Disease

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.

Evolutionary pathway to increased virulence and epidemic group A Streptococcus disease derived from 3,615 genome sequences

“…The molecular events included phage-mediated virulence gene acquisition, single nucleotide variant accumulation, and horizontal transfer of the 36-kb region encoding the virulence factors Nga and Slo (61)(62)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72)(73), likely mediated by generalized transduction (24). It is now clear from our analysis that a complex multistep (9).…”

TheStreptococcus pyogenesCapsule Is Required for Adhesion of Bacteria to Virus-Infected Alveolar Epithelial Cells and Lethal Bacterial-Viral Superinfection

“…SLO hemolytic assays were carried out essentially as described by Limbago et al (26). Briefly, an overnight culture of test strains was adjusted to an absorbance of 1.0 at 600 nm, after which the supernatant was separated by centrifugation for 10 min at 7,500 ϫ g and then filtered (pore size, 0.25 m).…”

“…In addition, another GAS virulence factor, streptolysin O (SLO), which binds to cholesterol in red blood cell membranes, causing lysis, reportedly exerts various neurological effects, increases capillary permeability, and induces dermal necrosis in rabbits (1). On the other hand, direct studies of the role of SLO during infection recently revealed that the contribution of SLO to GAS virulence was limited in a murine dermonecrosis invasive infection model (26). Still another factor is streptolysin S (SLS), which like SLO is potently cytolytic (1).…”

Identification of a Streptolysin S-Associated Gene Cluster and Its Role in the Pathogenesis ofStreptococcus iniaeDisease

“…Hemolysins, or cytolysins, are well-recognized features of many bacterial species, including streptococci, and are generally associated with damage to the membranes of a variety of mammalian cell types. Examples of streptococcal cytolysins include streptolysin O (SLO) and streptolysin S (SLS) of group A streptococci (GAS), the beta-hemolysin/cytolysin of group B streptococci (GBS), and the pneumolysin of Streptococcus pneumoniae, each of which has been implicated as a virulence factor in animal models of infection (3,4,33,49). In this investigation, we describe a molecular approach used to identify the genetic locus responsible for cytolysin production in S. iniae.…”