Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA.
Microbiology (Reading). 2010 Jun;156(Pt 6):1589-1599. doi: 10.1099/mic.0.035642-0. Epub 2010 Feb 11.
Reuterin is an antimicrobial compound produced by Lactobacillus reuteri, and has been proposed to mediate, in part, the probiotic health benefits ascribed to this micro-organism. Despite 20 years of investigation, the mechanism of action by which reuterin exerts its antimicrobial effects has remained elusive. Here we provide evidence that reuterin induces oxidative stress in cells, most likely by modifying thiol groups in proteins and small molecules. Escherichia coli cells subjected to sublethal levels of reuterin expressed a set of genes that overlapped with the set of genes composing the OxyR regulon, which senses and responds to various forms of oxidative stress. E. coli cells mutated for oxyR were more sensitive to reuterin compared with wild-type cells, further supporting a role for reuterin in exerting oxidative stress. The addition of cysteine to E. coli or Clostridium difficile growth media prior to exposure to reuterin suppressed the antimicrobial effect of reuterin on these bacteria. Interestingly, interaction with E. coli stimulated reuterin production or secretion by L. reuteri, indicating that contact with other microbes in the gut increases reuterin output. Thus, reuterin inhibits bacterial growth by modifying thiol groups, which indicates that reuterin negatively affects a large number of cellular targets.
雷替曲塞是由罗伊氏乳杆菌产生的一种抗菌化合物，它被认为介导了部分益生菌的健康益处，这些益处归因于这种微生物。尽管经过了 20 年的研究，但雷替曲塞发挥其抗菌作用的机制仍然难以捉摸。在这里，我们提供的证据表明，雷替曲塞诱导细胞产生氧化应激，很可能是通过修饰蛋白质和小分子中的巯基基团。暴露于亚致死水平雷替曲塞的大肠杆菌细胞表达了一组与构成 OxyR 调控子的一组基因重叠的基因，该调控子感知和响应各种形式的氧化应激。与野生型细胞相比，oxyR 突变的大肠杆菌细胞对雷替曲塞更敏感，这进一步支持了雷替曲塞在发挥氧化应激作用中的作用。在暴露于雷替曲塞之前，向大肠杆菌或艰难梭菌的生长培养基中添加半胱氨酸，可抑制雷替曲塞对这些细菌的抗菌作用。有趣的是，与大肠杆菌的相互作用刺激了雷替曲塞的产生或分泌，表明与肠道中的其他微生物接触会增加雷替曲塞的产量。因此，雷替曲塞通过修饰巯基基团抑制细菌生长，这表明雷替曲塞对大量细胞靶标产生负面影响。
