Streptococcus pyogenes Hijacks Host Glutathione for Growth and Innate Immune Evasion
Stephan Brouwer, Magnus G. Jespersen, Cheryl‐lynn Y. Ong, David M. P. De Oliveira, Bernhard Keller, Amanda J. Cork, Karrera Y. Djoko, Mark R. Davies, Mark J. Walker
Abstract
During infection, microbes must escape host immune responses and survive exposure to reactive oxygen species produced by immune cells. Here, we identify the ABC transporter substrate binding protein GshT as a key component of the glutathione salvage pathway in glutathione-auxotrophic GAS. Host-acquired glutathione is crucial to the GAS antioxidant defense system, facilitating escape from the host innate immune response. This study demonstrates a direct link between glutathione assimilation, aerobic metabolism, and virulence factor production in an important human pathogen. Our findings provide mechanistic insight into host adaptation that enables extracellular bacterial pathogens such as GAS to exploit the abundance of glutathione in the host cytosol for their own benefit.