Article
Requirement and Synergistic Contribution of PAF acetylhydrolase Sse and Streptolysin S to Inhibition of Neutrophil Recruitment and Systemic Infection by Hypervirulent emm3 Group A Streptococcus...
Authors
Wenchao Feng, Dylan Minor, Mengyao Liu, Benfang Lei
Publication
Infection and Immunity
Abstract
Hypervirulent Group A Streptococcus (GAS) can inhibit neutrophil recruitment and cause systemic infection in mouse model of skin infection. The purpose of this study was to determine whether PAF 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 emm3 GAS strain. Deletions of sse and sagA in MGAS315 synergistically reduced skin lesion size and GAS burden in the liver and spleen. However, the mutants were persistent at skin sites and had similar growth factors in nonimmune blood. Thus, the low ?sse?sagA numbers in the liver/spleen is likely due to its reduction in systemic dissemination. Few intact and necrotic neutrophils were detected at MGAS315 infection sites. In contrast, many neutrophils and necrotic cells were present at the edge of ?sse sites on day 1 and at the edge and inside of ?sse sites on day 2. ?sagA sites had massive and few intact neutrophils at the edge and center of infection sites, respectively, on day 1 and were full of intact neutrophils or necrotic cells on Day 2. ?sse?sagA sites had massive intact neutrophils in the whole infection sites. These sse and sagA deletion-caused changes in the histological pattern at skin infection sites can be complemented. Thus, sse and sagA deletions synergistically enhance neutrophil recruitment. These findings indicate that Sse and SLS are both required but neither is sufficient for inhibition of neutrophil recruitment and systemic infection by hypervirulent GAS.
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