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用基因编辑工具装载的生物模拟阴性囊泡,具有高效的细菌内部化,用于体内根除病原体

Xueli Jia^1,2, Bochuan Yuan³, Wanmei Wang¹

¹Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing, 100850, China.

Journal of nanobiotechnology

|December 22, 2024

概括

生物模拟阴性杂交囊泡提供CRISPR/Cas9等离子体来对抗抗药性细菌,如Acinetobacter baumannii和Pseudomonas aeruginosa,提供了一种新的抗菌战略. 这种方法绕过了传统的抗生素耐药性机制,以有效地根除感染.

科学领域:

微生物学微生物学
生物技术是生物技术.
传染性疾病传染性疾病

背景情况:

耐药性细菌感染,包括多抗药性Acinetobacter baumannii (MRAB) 和耐药性Pseudomonas aeruginosa (DRPA),是COVID-19后的主要死亡原因.
经典的抗生素策略受到细菌耐药性日益增长的挑战的限制.

研究的目的:

开发一种使用CRISPR/Cas9等离子体输送的新型抗菌策略,以对抗耐药细菌感染.
为了克服在感染部位向病原体输送大型负电荷的CRISPR/Cas9等离子体的挑战.

主要方法:

设计用于在MRAB或DRPA内复制并诱导染色体损伤的CRISPR/Cas9等离子体的构建.
生物模拟阴阳性混合囊泡 (BCV) 的开发,将细菌外膜囊泡和阴阳性脂质整合起来,以有效地输送等离子体.
在体外和体内测试BCV介导的等离子体输送和随后的MRAB和DRPA感染的根除.

主要成果:

在体外和体内,BCV证明了CRISPR/Cas9等离子体的有效输送和内部化到MRAB和DRPA.
在内或局部应用BCVs水凝成功根除了MRAB肺部感染和DRPA伤口感染.
装有CRISPR/Cas9等离子体的BCV在消除感染肺和伤口中的向病原体方面被证明是有效的.

结论:

载有CRISPR/Cas9等离子体的BCV代表了一种有希望的,不依赖于耐药性的治疗方法,用于治疗耐药性细菌感染.
这种新的传递系统克服了以前在向细菌病原体传递大量遗传有效载荷方面的局限性.
该战略显示了治疗多药耐药Acinetobacter baumannii和耐药Pseudomonas aeruginosa引起的严重感染的潜力.

关键词:

这种细菌是Acinetobacter baumannii.伪omonas空气菌伪omonas空气菌这是一种CRISPR/Cas9等离子体.阴阳性脂质阴阳性脂质外膜囊泡的外膜囊泡是什么?肺部感染肺部感染伤口感染伤口感染

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