Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA; Department of Chemistry, Yale University, New Haven, CT 06520, USA; Microbial Sciences Institute, Yale University, West Haven, CT 06516, USA.
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA; Microbial Sciences Institute, Yale University, West Haven, CT 06516, USA.
Cell. 2022 Nov 23;185(24):4526-4540.e18. doi: 10.1016/j.cell.2022.10.008. Epub 2022 Nov 7.
Low-molecular-weight (LMW) thiols are small-molecule antioxidants required for the maintenance of intracellular redox homeostasis. However, many host-associated microbes, including the gastric pathogen Helicobacter pylori, unexpectedly lack LMW-thiol biosynthetic pathways. Using reactivity-guided metabolomics, we identified the unusual LMW thiol ergothioneine (EGT) in H. pylori. Dietary EGT accumulates to millimolar levels in human tissues and has been broadly implicated in mitigating disease risk. Although certain microorganisms synthesize EGT, we discovered that H. pylori acquires this LMW thiol from the host environment using a highly selective ATP-binding cassette transporter-EgtUV. EgtUV confers a competitive colonization advantage in vivo and is widely conserved in gastrointestinal microbes. Furthermore, we found that human fecal bacteria metabolize EGT, which may contribute to production of the disease-associated metabolite trimethylamine N-oxide. Collectively, our findings illustrate a previously unappreciated mechanism of microbial redox regulation in the gut and suggest that inter-kingdom competition for dietary EGT may broadly impact human health.
低分子量（LMW）硫醇是维持细胞内氧化还原平衡所必需的小分子抗氧化剂。然而，许多与宿主相关的微生物，包括胃病原体幽门螺杆菌，出人意料地缺乏 LMW-硫醇生物合成途径。我们使用反应性导向代谢组学，在 H. pylori 中鉴定了不寻常的 LMW 硫醇麦硫因（EGT）。膳食 EGT 在人体组织中积累到毫摩尔水平，广泛涉及减轻疾病风险。尽管某些微生物合成 EGT，但我们发现 H. pylori 使用高度选择性的 ATP 结合盒转运蛋白-EgtUV 从宿主环境中获取这种 LMW 硫醇。EgtUV 在体内赋予竞争定植优势，并且在胃肠道微生物中广泛保守。此外，我们发现人类粪便细菌代谢 EGT，这可能有助于产生与疾病相关的代谢物三甲胺 N-氧化物。总之，我们的研究结果说明了肠道中微生物氧化还原调节的一个以前未被认识的机制，并表明对膳食 EGT 的种间竞争可能广泛影响人类健康。
