Department of Pathology & Immunology, Baylor College of Medicine , Houston, TX, USA.
Department of Molecular Virology and Microbiology, Baylor College of Medicine , Houston, TX, USA.
Gut Microbes. 2020 Nov 9;12(1):1788898. doi: 10.1080/19490976.2020.1795388.
Antibiotic resistance is one of the world's greatest public health challenges and adjunct probiotic therapies are strategies that could lessen this burden. infection (CDI) is a prime example where adjunct probiotic therapies could decrease disease incidence through prevention. Human-derived is a probiotic that produces the antimicrobial compound reuterin known to prevent colonization of antibiotic-treated fecal microbial communities. However, the mechanism of inhibition is unclear. We show that reuterin inhibits outgrowth from spores and vegetative cell growth, however, no effect on germination or sporulation was observed. Consistent with published studies, we found that exposure to reuterin stimulated reactive oxygen species (ROS) in , resulting in a concentration-dependent reduction in cell viability that was rescued by the antioxidant glutathione. Sublethal concentrations of reuterin enhanced the susceptibility of vegetative to vancomycin and metronidazole treatment and reduced toxin synthesis by . We also demonstrate that reuterin is protective against toxin-mediated cellular damage in the human intestinal enteroid model. Overall, our results indicate that ROS are essential mediators of reuterin activity and show that reuterin production by is compatible as a therapeutic in a clinically relevant model.
抗生素耐药性是全球面临的最大公共卫生挑战之一，辅助益生菌疗法是减轻这一负担的策略之一。艰难梭菌感染 (CDI) 就是一个很好的例子，辅助益生菌疗法可以通过预防来降低疾病发病率。人源 是一种益生菌，它能产生抗菌化合物雷替辛，已知可预防抗生素处理的粪便微生物群落中 的定植。然而，抑制机制尚不清楚。我们发现雷替辛抑制 的孢子和营养细胞生长，但对 萌发或孢子形成没有影响。与已发表的研究一致，我们发现雷替辛刺激 中的活性氧 (ROS)，导致细胞活力的浓度依赖性降低，抗氧化剂谷胱甘肽可挽救这种降低。亚致死浓度的雷替辛增强了 对万古霉素和甲硝唑治疗的敏感性，并减少了 的毒素合成。我们还证明雷替辛可防止 毒素介导的人肠类器官模型中的细胞损伤。总的来说，我们的结果表明 ROS 是雷替辛活性的重要介质，并表明 在临床相关模型中作为治疗剂是可行的。
