Review Article REVIEW ARTICLE Mechanisms of group A Streptococcus resistance to reactive oxygen species

One sentence summary: This review discusses the mechanisms utilized by the bacterial pathogen group A Streptococcus to detoxify reactive oxygen species and survive in the human host under conditions of oxidative stress. Editor: Birgitta Henriques Normark Streptococcus pyogenes, also known as group A Streptococcus (GAS), is an exclusively human Gram-positive bacterial pathogen ranked among the ‘top 10 ’ causes of infection-related deaths worldwide. GAS commonly causes benign and self-limiting epithelial infections (pharyngitis and impetigo), and less frequent severe invasive diseases (bacteremia, toxic shock syndrome and necrotizing fasciitis). Annually, GAS causes 700 million infections, including 1.8 million invasive infections with a mortality rate of 25%. In order to establish an infection, GAS must counteract the oxidative stress conditions generated by the release of reactive oxygen species (ROS) at the infection site by host immune cells such as neutrophils and monocytes. ROS are the highly reactive and toxic byproducts of oxygen metabolism, including hydrogen peroxide (H2O2), superoxide anion (O2 −), hydroxyl radicals (OH ) and singlet oxygen (O2∗), which can damage bacterial nucleic acids, proteins and cell membranes. This review summarizes the enzymatic and regulatory mechanisms utilized by GAS to thwar