H2S:在细菌中对抗生素的普遍防御
Konstantin Shatalin1, Elena Shatalina, Alexander Mironov
1Department of Biochemistry, New York University School of Medicine, New York, NY 10016, USA.
Science (New York, N.Y.)
|November 19, 2011
概括
细菌中的硫化 (H2S) 生产对于抗生素耐药性至关重要. 抑制H(2) S合成通过降低氧化应激缓解,增加了病原体对抗生素的敏感性.
科学领域:
- 微生物学 微生物学
- 生物化学 生物化学
- 病原体研究 病原体研究
背景情况:
- Prokaryotic 硫化 (H(2) S 生产是常见的,但其在非硫细菌中的生理作用尚不清楚.
- 抗生素耐药性是一个日益严重的全球健康问题,需要新的治疗策略.
研究的目的:
- 研究H(2) S在细菌生理学中的作用及其对抗生素耐药性的影响.
- 阐明涉及H(2) S生产的生物化学途径及其与抗生素敏感性的联系.
主要方法:
- 关键酶 (cystathionine β-synthase,cystathionine γ-lyase,3-mercaptopyruvate sulfurtransferase) 的遗传失活化发生在Bacillus anthracis,Pseudomonas aeruginosa,金黄色葡萄球菌和大肠杆菌中.
- 评估H(2) S生产,抗生素敏感性和氧化应激水平.
- 对H(2) S和氧化对细菌生长的协同作用的评估.
主要成果:
- 产生H(2) S的酶的失活使主要的细菌病原体对各种抗生素高度敏感.
- 外源的H2S添加恢复了H2S缺乏突变体的抗生素耐药性.
- 发现硫化和氧化可以协同作用,维持细菌生长.
- 抗生素耐药性的机制涉及H(2) S介导的抗生素诱导的氧化应激的缓解.
结论:
- 硫化在细菌抗生素耐药性方面发挥着重要的生理作用.
- 准H(2) S生产途径可能是对抗抗生素耐药性病原体的可行策略.
- 氧化氧化物,氧化物和氧化应激之间的相互作用对细菌的生存和生长至关重要.
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