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Laura M Cersosimo1, Madeline Graham1, Auriane Monestier2,3
1Massachusetts Host-Microbiome Center, Dept. Pathology, Brigham & Women's Hospital, Harvard Medical School. Boston, MA 02115.
bioRxiv : the preprint server for biology
|June 9, 2023
概括
克洛斯特里迪奥伊德困难蛋白质代谢对于肠道殖民和毒性至关重要. 扰乱林减少酶会延迟病原体的生长和毒素的产生,影响疾病的严重程度.
科学领域:
- 微生物学 微生物学
- 病原体的新陈代谢
- 肠道微生物组的动力学
背景情况:
- 困难菌 (C. diff) 是 nosocomial 感染的主要原因,通常是在抗生素诱导的肠道失生症之后.
- C. diff利用氨基酸的Stickland发酵来获取能量,其中素是主要的还原基质.
- 了解C. diff在肠道中的代谢适应对于开发向疗法至关重要.
研究的目的:
- 在体内研究减少性普罗林代谢在C. difficile毒性中所起的作用.
- 了解氨酸代谢如何影响病原体的殖民,生长和毒素的产生.
主要方法:
- 在 gnotobiotic 小鼠中比较野生型和缺乏proline 减少酶 (ΔprdB) 的 C. difficile 菌株 (ATCC43255).
- 在体内转录组分析以评估代谢途径的改变.
主要成果:
- 受 ΔprdB 突变病毒感染的小鼠表现出延迟的殖民化,生长和毒素生产,导致延长生存时间.
- 林减少酶的缺失破坏了多种代谢途径,包括氧化性Stickland途径和鸟类素转换.
- 这些干扰导致了 ΔprdB 突变体的生长,分泌和毒素生成的减少.
结论:
- 氨酸还原酶对于支持早期C.diff殖民和随后的毒性至关重要.
- 准普罗林代谢提供了一个潜在的策略,以减轻C.diff的病变发生.
- 代谢灵活性,特别是素利用,是C. diff感染和引起疾病的能力的一个关键因素.
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