RNAseq transcriptome analysis of Streptococcus pyogenes HKU16 and an isogenic gshT mutant. Manuscript title: Streptococcus pyogenes hijacks host glutathione for growth and innate immune evasion

The nasopharynx and the skin are the major oxygen-rich anatomical sites for colonization by the human pathogen Streptococcus pyogenes (group A Streptococcus, GAS). To establish infection, GAS must survive oxidative stress generated during aerobic metabolism and the release of reactive oxygen species (ROS) by host innate immune cells. Glutathione is the major host antioxidant molecule while GAS is glutathione-auxotrophic. Here we report the molecular characterization of the ABC transporter substrate binding protein GshT in the GAS glutathione salvage pathway. We demonstrate that glutathione uptake is critical for aerobic growth of GAS and that impaired import of glutathione induces oxidative stress that triggers enhanced production of the reducing equivalent NADPH. Our results highlight the interrelationship between glutathione assimilation, carbohydrate metabolism, virulence factor production and innate immune evasion. Together, these findings suggest an adaptive strategy employed by extracellular bacterial pathogens to exploit host glutathione stores for their own benefit. Bacteria were grown to late-logarithmic growth phase in Todd Hewitt broth supplemented with 1% yeast extract (THY). 3 biological replicates for each strain, HKU16 wildtype and gshT mutant.