13 Jan 2023
by Richa

Summary- paper 4: A microbial transporter of the dietary antioxidant ergothioneine

Daniel G. Dumitrescu, Elizabeth M. Gordon, Yekaterina Kovalyova, Anna B. Seminara, Brianna Duncan-Lowey, Emily R. Forster, Wen Zhou, Carmen J. Booth, Aimee Shen ,Philip J. Kranzusch, Stavroula K. Hatzios

Cell, 2022

Questions/gaps addressed:

  • Low-molecular-weight (LMW) thiols such as Glutathione are key to maintaining redox balance. Helicobacter pylori (gastric pathogen) lacks enzymes to synthesize LMW thiols. How does it maintain intracellular redox homeostasis without producing known LMW thiols, despite persistent exposure to ROS in the host?

Major hypotheses:

  • H. pylori must have mechanisms such as a transporter to obtain LMW thiols from the host.

Key methods:

  • reactivity-guided metabolomics screen to identify LMW thiols in H. pylori, wherein bacterial cell extracts were treated with the thiol-alkylating agent monobromobimane (mBBr)

  • crystal structure of EGT bound to EgtU transporter

Major takeaways:

  • Metabolomic screen identified ergothioneine (EGT) is present in H. pylori. EGT is a sulfur-containing derivative of histidine, stable under physiological conditions, only synthesized by bacteria (no H pylori) and fungi (so come via diet).

  • H. pylori also lacks the mammalian EGT transporter (OCTN1) ortholog.

  • EGT structure resembles bacterial osmolyte glycine betaine. Found that betaine transporters EgtUV can also import EGT.

  • Presence of these EgtUV transporters provides H. pylori competive colonization advantage. These transporters are conserved in GI microbes.