Contribution of Glutathione Peroxidase to the Virulence of Streptococcus pyogenes

Abstract

Glutathione peroxidases are widespread among eukaryotic organisms and function as a major defense against hydrogen peroxide and organic peroxides. However, glutathione peroxidases are not well studied among prokaryotic organisms and have not previously been shown to promote bacterial virulence. Recently, a gene with homology to glutathione peroxidase was shown to contribute to the antioxidant defenses of Streptococcus pyogenes (group A streptococcus). Since this bacterium causes numerous suppurative diseases that require it to thrive in highly inflamed tissue, it was of interest to determine if glutathione peroxidase is important for virulence. In this study, we report that GpoA glutathione peroxidase is the major glutathione peroxidase in S. pyogenes and is essential for S. pyogenes pathogenesis in several murine models that mimic different aspects of streptococcal suppurative disease. In contrast, glutathione peroxidase is not essential for virulence in a zebrafish model of streptococcal myositis, a disease characterized by the absence of an inflammatory cell infiltrate. Taken together, these data suggest that S. pyogenes requires glutathione peroxidase to adapt to oxidative stress that accompanies an inflammatory response, and the data provide the first demonstration of a role for glutathione peroxidase in bacterial virulence. The fact that genes encoding putative glutathione peroxidases are found in the genomes of many pathogenic bacterial species suggests that glutathione peroxidase may have a general role in bacterial pathogenesis.

Regulation of SpeB inStreptococcus pyogenesby pH and NaCl: a Model for In Vivo Gene Expression

“…For isolation of RNA from in vivo-grown bacteria, groups of outbred, immunocompetent, hairless female mice (Jackson Laboratories) were used for subcutaneous injection of midexponential phase inocula of strain HSC5 (approximately 10 7 CFU) as described previously (4). At 1, 2, or 3 days postinoculation the mice were sacrificed and the dermis and underlying soft tissues at the site of infection from at least five animals were harvested, pooled, and partially homogenized as described previously (4). Extracts were prepared by organic extraction and chaotropic disruption (RNeasy lipid tissue kit; QIAGEN).…”

“…To investigate this issue, RNA was isolated from infected mouse tissue at various time points and transcript abundance of speB was determined by real-time RT-PCR. For S. pyogenes strain HSC5, the kinetics of ulcer development have been described in detail elsewhere (4). Briefly, at 8 to 12 h postinfection, this strain produces a well-defined area of inflammation that is characterized by the recruitment of large numbers of neutrophils.…”

Stress Physiology of Lactic Acid Bacteria

“…Loss of alkylhydroperoxidase activity attenuated pneumococcal virulence in cutaneous, pneumonia, and bacteremia models (523). The third characterized streptococcal peroxidase, glutathione peroxidase (GpoA), is essential for GAS pathogenesis in several murine models that mimic suppurative diseases but not in a zebrafish streptococcal myositis model characterized by the absence of inflammation (524). In contrast to streptococci, E. faecalis contains the heme-dependent catalase KatA, which is activated by heme taken up from the environment (259); its implication for virulence has not yet been investigated.…”

Defenses against Oxidative Stress inNeisseria gonorrhoeae: a System Tailored for a Challenging Environment

“…Defenses against oxidative stress are increasingly being recognized as playing an important role in virulence (28,67,102,105,123,206,251,258). A greater understanding of the oxidative stress response of microbial pathogens may aid the future development of treatment and prevention strategies for disease caused by these bacteria.…”