科学者が腸内細菌の食習慣を模倣して一般的な胃腸疾患を解明(Yale scientists imitate a bacterium’s eating habits to unravel a common stomach bug)

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2025-03-10 イェール大学

イェール大学の研究チームは、胃に生息するヘリコバクター・ピロリ(H. pylori)の栄養摂取メカニズムを解明するため、新たな培養技術を開発した。H. pyloriは一部の人で消化性潰瘍や胃がんの原因となるが、その栄養要求性は不明点が多かった。研究者は、細菌が摂取するエルゴチオネイン(EGT)に着目し、EGTなしで培養できる技術を開発。これにより、EGTが細菌の成長や生存に与える影響を詳細に分析可能となった。この成果は、H. pyloriの生存戦略の理解を深め、胃腸疾患の新たな治療法開発につながる可能性がある。

<関連情報>

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

科学者が腸内細菌の食習慣を模倣して一般的な胃腸疾患を解明(Yale scientists imitate a bacterium’s eating habits to unravel a common stomach bug)

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.

医療・健康
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