Cytocidal Effect ofStreptococcus pyogeneson Mouse Neutrophils In Vivo and the Critical Role of Streptolysin S

Abstract

We analyzed the in vivo dynamics of peritoneal exudate cells (PECs) in mice injected with group A streptococcus (GAS). A live low-virulence strain, as well as heat-killed low- and high-virulence strains, significantly increased the number of PECs (primarily neutrophils), whereas a live high-virulence strain did not. When coinjected with thioglycollate, the live high-virulence strain, as well as most other GAS strains, suppressed the ability of thioglycollate to induce neutrophil exudation. This suppression was due to a cytocidal effect of GAS on exuded neutrophils rather than an inhibition of neutrophil migration. In addition, GAS enhanced the apoptosis of neutrophils. These cytocidal effects were significantly reduced by the deletion of functional streptolysin S from GAS. Our findings suggest that, in addition to the production of antiphagocytic factors and survival inside phagocytes, GAS uses a more aggressive method--the elimination of neutrophils--to evade the host's innate immune system.

Analysis of the Transcriptome of Group A Streptococcus in Mouse Soft Tissue Infection

“…17,59 In addition, high levels of expression of sagA (ranked 28th), which encodes the potent cytolysin SLS, was notable because SLS is thought to accelerate necrotic fascial injury through cytotoxic or apoptotic effects on many cell types including, but not limited to, neutrophils. 60 The untranslated mRNA of the pleiotropic effect locus (pel), which incidentally contains sagA, also acts as an antisense RNA transcriptional regulator, augmenting GAS virulence factor expression [SIC, M-protein, extracellular NAD-glycohydrolase (NADase encoded by nga/spn), plasminogen activator streptokinase encoded by ska, and SpeB] when pel RNA expression is induced. 61,62 We detected abundant sagA transcripts; thus pel-induced virulence gene expression may be predicted, as was observed in this study for all but nga (ranked 780th in WT extracts).…”

Implementation of a Permeable Membrane Insert-based Infection System to Study the Effects of Secreted Bacterial Toxins on Mammalian Host Cells

“…Many bacterial pathogens actively secrete toxins and other soluble factors to aid in the destruction of host tissue, to initiate signaling changes in host cells or to manipulate immune system responses during the course of infection [1][2][3][4][5][6][7][8][9][10] . Though methods have been developed to successfully purify and produce many of these important virulence factors for study, some bacterial products have unique structures or extensive posttranslational modifications that make them recalcitrant candidates for purification methods and thus cannot be studied in isolation using in vitro systems.…”

Systems Biology Approach to Identifying Host Interactive Pathways Modulating the Severity of Streptococcal Sepsis

“…By contrast, several genes associated with pro-and anti-apoptotic response were differentially expressed in the selected susceptible and resistant strains post-infection (Figure 3-5). Apoptosis in streptococcal pathogenesis is affected by interacting factors including, context of infection (Marriott and Dockrell, 2006), cells undergoing apoptosis (Kobayashi et al, 2003;Nakagawa et al, 2004;Miyoshi-Akiyama et al, 2005), for example, apoptosis aids in the clearing of infection if macrophages are undergoing apoptosis, while it would be harmful to the host if lymphocytes are undergoing apoptosis. Other factors include, whether the bacteria is internalized or extracellular (Cywes Bentley et al, 2005) and accordingly the type of apoptosis pathways activated (Klenk et al, 2005).…”