Streptococcus pyogenes Hijacks Host Glutathione for Growth and Innate Immune Evasion

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.

A newly identified flavoprotein disulfide reductase Har protects Streptococcus pneumoniae against hypothiocyanous acid

“…This finding suggests that the reductase enzyme may be upregulated when GSH utilization is compromised. Alternatively, increased reductase activity in the GSH mutants could point to higher NADPH/NADH levels as previously observed by deleting GshT in Streptococcus pyogenes (50). Increased HOSCN reductase activity in the S. pneumoniae Δgor mutant might also explain why we previously found this strain to survive equally well as the WT following exposure to reagent HOSCN in Hank's buffered saline, despite its inability to recycle oxidized GSH (21).…”

Detection of Streptococcus pyogenes M1UK in Australia and characterization of the mutation driving enhanced expression of superantigen SpeA

“…Total RNA was routinely isolated from bacterial cells using the RNeasy minikit (Qiagen) as previously described 67 . In brief, S. pyogenes strains were grown in THY medium to an OD 600 of ~0.8.…”

Host-Mediated Copper Stress Is Not Protective against Streptococcus pneumoniae D39 Infection

“…The lack of an alternative thiol pool may also explain the growth perturbation of the Δ gshT strain in the absence of Cu stress in vitro , which is likely the result of the alternative cellular functions fulfilled by GSH. These functions include the buffering of other metal ions, oxidative stress management, and cellular redox homeostasis ( 30 , 37 , 59 , 60 ). Interestingly, the reduced cellular density of Δ gshT in vitro does not appear to hinder the replication or invasiveness of this strain in the bacteremia model in vivo .…”