Host-to-Host Group A Streptococcus Transmission Causes Infection of the Lamina Propria but Not Epithelium of the Upper Respiratory Tract in MyD88-Deficient Mice.

To understand protective immune responses against the onset of group A Streptococcus respiratory infection, we investigated whether MyD88 KO mice were susceptible to acute infection through transmission. After commingling with mice that had intranasal group A Streptococcus (GAS) inoculation, MyD88 recipient mice had increased GAS loads in the nasal cavity and throat that reached a mean throat colonization of 6.3 × 10 CFU/swab and mean GAS load of 5.

Tissue Tropism in Streptococcal Infection: Wild-Type M1T1 Group A Is Efficiently Cleared by Neutrophils Using an NADPH Oxidase-Dependent Mechanism in the Lung but Not in the Skin.

Group A (GAS) commonly causes pharyngitis and skin infections. Little is known why streptococcal pharyngitis usually does not lead to pneumonia and why the skin is a favorite niche for GAS. To partially address these questions, the effectiveness of neutrophils in clearing wild-type (wt) M1T1 GAS strain MGAS2221 from the lung and from the skin was examined in murine models of intratracheal pneumonia and subcutaneous infection.

Hypervirulent Group A Streptococcus of Genotype 3 Invades the Vascular System in Pulmonary Infection of Mice.

Natural mutations of the two-component regulatory system CovRS are frequently associated with invasive group A (GAS) isolates and lead to the enhancement of virulence gene expression, innate immune evasion, systemic dissemination, and virulence. How CovRS mutations enhance systemic dissemination is not well understood. A hypervirulent GAS isolate of the 3 genotype, MGAS315, was characterized using a mouse model of pulmonary infection to understand systemic dissemination.

Requirement and Synergistic Contribution of Platelet-Activating Factor Acetylhydrolase Sse and Streptolysin S to Inhibition of Neutrophil Recruitment and Systemic Infection by Hypervirulent Group A Streptococcus in Subcutaneous Infection of Mice.

Hypervirulent group A streptococcus (GAS) can inhibit neutrophil recruitment and cause systemic infection in a mouse model of skin infection. The purpose of this study was to determine whether platelet-activating factor acetylhydrolase Sse and streptolysin S (SLS) have synergistic contributions to inhibition of neutrophil recruitment and systemic infection in subcutaneous infection of mice by MGAS315, a hypervirulent genotype GAS strain. Deletion of and in MGAS315 synergistically reduced the skin lesion size and GAS burden in the liver and spleen.

Null Mutations of Group A Streptococcus Orphan Kinase RocA: Selection in Mouse Infection and Comparison with CovS Mutations in Alteration of In Vitro and In Vivo Protease SpeB Expression and Virulence.

Group A Streptococcus (GAS) acquires mutations of the virulence regulator CovRS in human and mouse infections, and these mutations result in the upregulation of virulence genes and the downregulation of the protease SpeB. To identify in vivo mutants with novel phenotypes, GAS isolates from infected mice were screened by enzymatic assays for SpeB and the platelet-activating factor acetylhydrolase Sse, and a new type of variant that had enhanced Sse expression and normal levels of SpeB production was identified (the variants had a phenotype referred to as enhanced Sse activity [Sse] and normal SpeB activity [SpeB]). Sse SpeB variants had transcript levels of CovRS-controlled virulence genes comparable to those of a covS mutant but had no covRS mutations.