微生物衍生的胆酸甲基酸及其表基因抑制了 Clostridioides difficile 的生长和致病性,同时保护了肠道微生物群的成员
Samantha C Kisthardt1, Rajani Thanissery1, Colleen M Pike1
1Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University , Raleigh, North Carolina, USA.
Journal of bacteriology
|September 11, 2023
概括
胆酸表皮剂,隔离甲酸 (iLCA) 和隔离甲酸 (iaLCA),有效地抑制了Clostridioides difficile的生长和毒素的表达. 这些化合物显示出作为向治疗的前景,对有益的肠道微生物群的影响最小.
科学领域:
- 微生物学 微生物学
- 胃肠病学 胃肠病学
- 药理学 药理学是指药理学的学科.
背景情况:
- 艰难结肠杆菌感染 (CDI) 是与使用抗生素破坏肠道微生物群和减少保护性胆汁酸相关的重大健康问题.
- 二次性胆酸,如石灰酸 (LCA) 和其表皮分离石灰酸 (iLCA),表现出对C. difficile的抑制作用.
研究的目的:
- 调查LCA及其表皮体 (iLCA,iaLCA) 对C. difficile的抑制机制.
- 评估这些胆汁酸对C. difficile生长,毒素产生和宿主细胞细胞毒性的影响.
主要方法:
- 最低抑制度 (MIC) 测试针对C. difficile和一个开始性肠道微生物群小组.
- 杀菌试验,膜损伤评估和毒素表达/活性评估.
- 卡科-2细胞亡和活力测试以确定宿主细胞毒性.
主要成果:
- iLCA和iaLCA在体外显示出强大的抑制C. difficile的生长,节省了大多数Gram-阴性杂交体.
- 这些表层表现出杀菌活性,并造成了显著的细菌膜损伤.
- iLCA和iALCA降低了TcdA的表达,而LCA降低了毒素的活性.
结论:
- LCA 副类型 iLCA 和 iaLCA 是 C. difficile 的有效抑制剂,以不同的机制向生长和毒性因素.
- 这些胆汁酸代表了CDI的有希望的治疗候选者,提供了针对性的作用,对肠道微生物群的破坏最小.
- 需要进一步的研究,以优化这些胆汁酸的输送,用于肠道治疗应用.
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