亚利硫胺类药物通过硫酶独立的机制抑制结肠细菌的生长
Conor J Crawford1, Charles W E Tomlinson2,3,4, Christian Gunawan5
1Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Potsdam 14476, Germany.
概括
准细菌碳水化合物硫酸酶可以治疗炎症性肠病 (IBD). 然而,硫酸盐抑制剂意外地向脂类激酶,损害有益的肠道细菌,如Bacteroides,而不是预期的硫酸酶.
科学领域:
- 微生物学 微生物学
- 生物化学 生化学
- 胃肠病学 胃肠病学
背景情况:
- 细菌碳水化合物硫酸酶降解结肠粘素,导致炎症性肠病 (IBD).
- 在IBD中硫酶活性升高与疾病严重程度相关,表明它们是治疗点.
研究的目的:
- 为了评估酸硫酸盐作为细菌碳水化合物硫酸酶的选择性抑制剂.
- 为了识别人类肠道微生物群 (HGM) 中的酸硫酸盐的分子标.
主要方法:
- 对细菌硫酸酶的选,对和碳水化合物硫酸盐库进行选.
- 在硫酸甘氨酸上培养HGM物种.
- 热蛋白质形 (TPP) 用于识别蛋白质标.
主要成果:
- 阿里硫酸盐对纯化碳水化合物硫酸酶无效.
- 阿里硫酸盐在硫酸甘油上抑制了HGM物种的生长.
- TPP确定了一种脂类激酶是导致酸硫酸盐效应的非目标因子.
结论:
- 硫酸盐表现出意想不到的脱效应,抑制脂类激酶并损害有益的HGM细菌.
- 开发特定的碳水化合物硫酶抑制剂对于IBD治疗至关重要.
- 由于对肠道微生物群的潜在不良影响,需要谨慎使用酸化合物.
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