用于局部输送抗真菌剂的 Bacillus subtilis 经过工程设计
Veronica A Montgomery1, Ethan Cain2, Mark P Styczynski2
1Wallace H. Coulter Department of Biomedical Engineering at Emory University and Georgia Tech, Georgia Institute of Technology, Atlanta, GA, United States of America.
PloS one
|November 30, 2023
概括
研究人员设计了Bacillus subtilis,以增加抗真菌化合物生产,以获得更好的局部治疗. 然而,由于生长速度较慢,修改后的细菌对真菌生长的有效性降低了,这突显了代谢工程的权衡.
科学领域:
- 微生物学 微生物学
- 生物技术是生物技术.
- 皮肤病学 皮肤病学
背景情况:
- 真菌性皮肤感染影响全球人口的20-25%,需要有效的局部治疗.
- 目前的治疗方法需要定期应用,这可能导致患者的坚持不佳.
- 细菌细菌 (Bacillus subtilis) 是一种天然存在的皮肤细菌,具有抗真菌特性.
研究的目的:
- 改造 Bacillus subtilis 以提高抗真菌脂 iturin A. 的生产和输送.
- 开发一个更方便,更持久的局部抗真菌平台.
- 改善患者对真菌感染治疗方案的坚持.
主要方法:
- 通过过度表达DegQ调节器来增加它urin A的产量.
- 量化伊图林 使用高性能液体染色学 (HPLC) 制造.
- 通过吸收度测量和体外抗真菌活性对Trichophyton mentagrophytes进行评估细菌生长动力学.
主要成果:
- 工程化B. subtilis在伊图林A的生产中显示出超过200%的增加.
- 改造品种的生长速度较慢,但达到与原始品种相同的终端细胞密度.
- 尽管伊图林A水平较高,但在体外试验中,工程菌株在抑制真菌生长方面有效性降低.
结论:
- 对B. subtilis的代谢工程可以显著增强抗真菌化合物生产.
- 在工程菌株中减少细菌生长率可能会对抗真菌疗效产生负面影响.
- 在代谢工程中,为了有效的抗真菌平台,平衡化合物生产 (标位) 与其他因素,如生长率至关重要.
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