群A型 estreptococcal asparagine的新陈代谢调节了细菌的毒性
Abhinay Sharma1, Aparna Anand1, Miriam Ravins1
1Department of Microbiology and Molecular Genetics, The Institute for Medical Research, Israel-Canada (IMRIC), Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, 9112102, Israel.
甲型链球菌的毒性是由阿斯巴拉金 (Asn) 水平控制的. 增加ASN增强病毒性基因表达,影响细菌代谢,提供潜在的治疗点.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 生物化学 生化学
背景情况:
- 甲型链球菌 (GAS) 引起人类重大疾病.
- 气体毒性主要由CovR/S两组系统 (TCS) 调节.
- 了解气体毒性调节对于开发有效治疗方法至关重要.
研究的目的:
- 研究阿斯巴拉金 (Asn) 在调节GAS病毒性基因表达中的作用.
- 阐明GAS中Asn介导调节背后的分子机制.
- 评估针对抗GAS疗法的Asn稳态向的潜力.
主要方法:
- 在最小化学定义的介质中培养GAS,Asn度各不相同.
- 使用定量PCR分析基因转录.
- 执行代谢学,以评估细胞内代谢物变化.
- 在入侵性软组织感染的小鼠模型中评估细菌毒性.
主要成果:
- 阿斯巴拉金 (Asn) 的存在增加了GAS病毒性基因表达,以CovR-依赖的方式.
- 阿斯恩的可用性降低了阿斯巴拉金合成酶 (AsnA) 和阿斯恩载体 (GlnPQ) 的转录.
- 由于Asn的可用性而增加的细胞内ADP/ATP比率可能会通过CovS.减少CovR酸化.
- 缺乏AsnA,GlnPQ或阿斯巴拉金酶 (AsnB) 的突变体在小鼠模型中显示出病毒毒性降低.
结论:
- 阿斯巴拉金的稳态通过CovR/S系统显著影响GAS毒性.
- 准细菌Asn代谢是一种针对GAS感染的新型治疗策略.
- 在GAS中调节Asn的机制与瘤生长中的机制有相似之处,这表明了更广泛的治疗含义.
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