人体肠道细菌基因毒素可利巴丁化DNA
Matthew R Wilson1, Yindi Jiang1, Peter W Villalta2
1Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.
Science (New York, N.Y.)
|February 16, 2019
概括
一些肠道细菌产生胆肠杆菌素, 研究人员确定了其破坏DNA的机制, 揭示了异常的环结构和潜在的暴露生物标志物.
科学领域:
- 微生物学
- 遗传学
- 癌症研究
背景情况:
- 某些大肠杆菌菌株产生大肠杆菌素,这是一种与结直肠癌有关的基因毒素.
- 十多年来, colibactin 的化学结构和基因毒性机制一直难以理解.
研究的目的:
- 为了阐明 colibactin 的化学结构.
- 确定大肠杆菌素基因毒性的分子机制.
- 调查胆肠杆菌素在结直肠癌发病过程中的作用.
主要方法:
- 没有针对性的DNA吸附学方法.
- 化学合成用于表征.
- 用大肠杆菌殖民的人类细胞系和小鼠模型的分析
主要成果:
- 鉴定了一种由 colibactin 引起的共价DNA 变异.
- 确立了可利巴因通过电友性环素化DNA.
- 在小鼠中证明了 colibactin 代谢物形成,并提出了不稳定的中间添加物.
结论:
- 科利巴克的基因毒性机制涉及一种不寻常的电友环基化DNA.
- 这些发现为肠道微生物诱导的结肠直肠癌提供了机理性见解.
- 鉴定出一个潜在的 colibactin 暴露的生物标记.
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