在Streptococcus mutans中描述尼古丁胺氨酸二核酸生物合成途径和调节机制
Haojie Yu1,2, Dandan Shao3, Yuheng Zhao4
1Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China.
概括
突变性链球菌通过尼古丁酸救援和PnuC-NadR途径合成NAD+. 通过SmNiaR的监管会影响细菌的毒性和酸的产生,这对于牙损伤至关重要.
科学领域:
- 微生物学 微生物学
- 生物化学 生化学
- 分子生物学分子生物学
背景情况:
- 尼古丁胺胺氨基二核酸 (NAD+) 对于细胞代谢和能量生产至关重要.
- 在Streptococcus mutans中NAD+生物合成途径,这是一个关键的牙病原体,尚未完全理解.
- 了解这些途径对于开发针对S. mutans的有针对性的干预措施至关重要.
研究的目的:
- 为了阐明Streptococcus mutans UA159.9.中的NAD+生物合成途径.
- 确定和描述控制S. mutans中NAD+生产的调节机制.
- 评估NAD+平衡在S. mutans.病毒性中的作用.
主要方法:
- 全基因组查以确定NAD+生物合成途径.
- 尼古丁酸救援途径和PnuC-NadR途径的表征.
- 对尼古丁酸反应调节剂SmNiaR的分析,包括其DNA结合和乙化特性.
- 尼阿R基因的删除突变发生和细菌表型的评估 (增殖,酸性生产,生物膜形成).
- 在老鼠下模型中评估细菌毒性.
主要成果:
- 确定了尼古丁酸救援途径和S. mutans中NAD+生物合成的不完整PnuC-NadR途径.
- 发现SmNiaR是尼古丁酸通路的调节者,K97的乙化影响DNA结合和NAD+水平.
- 在S. mutans中删除niaR导致生长受损,酸生产减少,生物膜形成改变,以及体内毒性减弱.
- 证明由SmNiaR调节的NAD+恒温是S. mutans病毒性至关重要的.
结论:
- 通过SmNiaR调节NAD+恒温是Streptococcus mutans. cariogenic毒性的一个重要因素.
- 准NAD+生物合成途径是控制牙损伤的潜在策略.
- 对SmNiaR功能及其与NAD+代谢相互作用的进一步研究可能会产生新的治疗点.
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