2025-03-10 イェール大学
<関連情報>
- https://westcampus.yale.edu/news/2025-03-10-yale-scientists-imitate-a-bacteriums-eating-habits-to-unravel-common-stomach-bug
- https://www.cell.com/cell-chemical-biology/abstract/S2451-9456(25)00062-5
細菌生理学に対するエルゴチオネインの効果を評価するための親和性ベースの枯渇戦略 An affinity-based depletion strategy for evaluating the effects of ergothioneine on bacterial physiology
Anna B. Seminara∙ Stavroula K. Hatzios
Cell Chemical Biology Published:March 10, 2025
DOI:https://doi.org/10.1016/j.chembiol.2025.02.004
Graphical abstract
Significance
Ergothioneine (EGT) is a dietary antioxidant broadly associated with positive health effects in humans. Certain host-adapted bacteria can import EGT using a dedicated transporter, but it is largely unknown how EGT import shapes microbial physiology. This is in part because EGT is naturally present in the complex medium required to culture many EGT-importing pathogens and commensal microbes, including the human gastric pathogen Helicobacter pylori. Consequently, identifying bacterial genes and phenotypes activated by EGT exposure is complicated by the natural occurrence of EGT in the culture medium. Here, we report the development of an EGT-chelating resin that depletes EGT from a variety of biological media, enabling the discovery of EGT-induced genes and growth phenotypes in H. pylori. We found that the competitive growth advantage of WT H. pylori over a transporter-deficient mutant is EGT-dependent. Furthermore, by analyzing H. pylori gene expression in EGT-replete versus EGT-depleted medium, we identified EGT-induced genes encoding outer-membrane proteins that may regulate bacterial EGT content upstream of the inner-membrane-localized EGT transporter. Collectively, these findings establish a method for controlling bacterial exposure to EGT, which should be broadly useful for elucidating cellular responses to this antioxidant in other bacteria.
Highlights
- EgtU-resin depletes ergothioneine (EGT) from complex bacteriological growth media
- EGT increases competitive fitness of Helicobacter pylori in stationary phase
- RNA-seq of H. pylori in EGT-replete vs. depleted media identifies EGT-induced genes
- EGT-induced outer-membrane-transporter genes may regulate H. pylori EGT content
Summary
Ergothioneine (EGT) is a thiol-based antioxidant synthesized by certain fungal and bacterial species that is prevalent in the human diet. Recently, an EGT-specific transporter, EgtUV, was discovered in bacteria that are incapable of EGT biosynthesis, including the gastric pathogen Helicobacter pylori. However, EGT is naturally abundant in the complex media required to culture H. pylori and many other host-associated microbes, complicating efforts to understand how this molecule influences microbial physiology. Using the solute-binding domain of H. pylori EgtUV, we generated an EGT-chelating resin that depletes EGT from nutrient-rich media. We determined that wild-type H. pylori requires EGT to outcompete a transporter-deficient strain in vitro. Furthermore, EGT induces transcription of genes encoding outer-membrane transporters that may regulate intracellular EGT content upstream of the inner-membrane-localized EgtUV transporter. Our work establishes a method for tuning exposure to an abundant antioxidant in vitro, enabling future studies of EGT in diverse microbial strains and communities.
