دورية أكاديمية
Reuterin disrupts Clostridioides difficile metabolism and pathogenicity through reactive oxygen species generation
العنوان: | Reuterin disrupts Clostridioides difficile metabolism and pathogenicity through reactive oxygen species generation |
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المؤلفون: | Melinda A. Engevik, Heather A. Danhof, Ritu Shrestha, Alexandra L. Chang-Graham, Joseph M. Hyser, Anthony M. Haag, Mahmoud A. Mohammad, Robert A. Britton, James Versalovic, Joseph A. Sorg, Jennifer K. Spinler |
المصدر: | Gut Microbes, Vol 12, Iss 1 (2020) |
بيانات النشر: | Taylor & Francis Group, 2020. |
سنة النشر: | 2020 |
المجموعة: | LCC:Diseases of the digestive system. Gastroenterology |
مصطلحات موضوعية: | reuterin, probiotics, lactobacillus reuteri, clostridioides difficile, enteroids, organoids, oxidative stress, reactive oxygen species, metabolism, Diseases of the digestive system. Gastroenterology, RC799-869 |
الوصف: | Antibiotic resistance is one of the world’s greatest public health challenges and adjunct probiotic therapies are strategies that could lessen this burden. Clostridioides difficile infection (CDI) is a prime example where adjunct probiotic therapies could decrease disease incidence through prevention. Human-derived Lactobacillus reuteri is a probiotic that produces the antimicrobial compound reuterin known to prevent C. difficile colonization of antibiotic-treated fecal microbial communities. However, the mechanism of inhibition is unclear. We show that reuterin inhibits C. difficile outgrowth from spores and vegetative cell growth, however, no effect on C. difficile germination or sporulation was observed. Consistent with published studies, we found that exposure to reuterin stimulated reactive oxygen species (ROS) in C. difficile, 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 C. difficile to vancomycin and metronidazole treatment and reduced toxin synthesis by C. difficile. We also demonstrate that reuterin is protective against C. difficile 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 L. reuteri is compatible as a therapeutic in a clinically relevant model. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1949-0976 1949-0984 19490976 |
Relation: | https://doaj.org/toc/1949-0976; https://doaj.org/toc/1949-0984 |
DOI: | 10.1080/19490976.2020.1795388 |
URL الوصول: | https://doaj.org/article/548379f0ffcc4fa28d4b96b38d0cd042 |
رقم الأكسشن: | edsdoj.548379f0ffcc4fa28d4b96b38d0cd042 |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 19490976 19490984 |
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DOI: | 10.1080/19490976.2020.1795388 |