Streptococcus pyogenes Arginine and Citrulline Catabolism Promotes Infection and Modulates Innate Immunity

摘要: A bacterium's ability to acquire nutrients from its host during infection is an essential component of pathogenesis. For the Gram-positive pathogen Streptococcus pyogenes, catabolism amino acid arginine via deiminase (ADI) pathway supplements energy production and provides protection against stress in vitro. Its expression enhanced murine models infection, suggesting important role vivo. To gain insight into function ADI pathogenesis, virulence mutants defective each enzymes was examined. Mutants unable use (ΔArcA) or citrulline (ΔArcB) were attenuated for carriage a model asymptomatic mucosal colonization. However, inflammatory cutaneous tissue, ΔArcA mutant but ΔArcB hyperattenuated, revealing unexpected tissue-specific metabolism When mice arginine-dependent nitric oxide (iNOS(-/-)) infected with mutant, rescued, demonstrating that S. pyogenes utilize dispensable absence oxide-mediated innate immunity. This work demonstrates importance suggests novel mechanism by which uses modulate immunity through depletion nutrient.