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.

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.

Myasthenia gravis (MG) is an autoimmune disease mediated by antibodies to acetylcholine receptors (AChRs) or muscle specific tyrosine kinase (MuSK). While the frequent association of MG with thymoma in patients aged 40-60 years is well recognized, its occurrence in patients with lymphoma has not been well studied. We review the literature on the association of MG and lymphoid malignancies and report two new patients. MG can occur in a synchronous or non-synchronous fashion with lymphoma. The pathogenesis of MG in lymphoid malignancies is probably heterogeneous and likely relates to perturbations in the immune mechanisms that normally prevent the emergence of autoimmunity. These perturbations could be the result of the lymphoid malignancy per se, or its treatment.

CooD, the minor subunit of CS1 pili of enterotoxigenicEscherichia coli, is essential for the assembly of stable, functional pili. We previously proposed that CooD is a rate-limiting initiator of CS1 pilus assembly and predicted that the level of CooD expression should therefore determine the number of CS1 pili assembled on the cell surface. In this study, we confirm that CooD is required for the initiation of pilus assembly rather than for the stabilization of pili after they are assembled by demonstrating that specific modulation of cooD expression also modulates the number of CS1 pili on bacterial cells.

The Mga protein in B514Sm, a Streptococcus pyogenes strain isolated as a mouse pathogen, contains amino acid substitutions at conserved sites that render the protein defective. Replacement of mga50 with the functional homolog mga4.1 restored full expression of Mga-regulated proteins. Restoration of Mga function did not affect fibrinogen binding, nor did it affect virulence in several mouse models of group A streptococcus infection.