尼弗拉泰尔通过细胞外和细胞内抗菌活性降低了巨细胞中的沙门氏菌生存率
Tian Xie1,2, Guifeng Liu1,2, Jiayi Ma1,2
1Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agrifood Safety and Quality, Ministry of Agriculture of China, Yangzhou University , Yangzhou, China.
Microbiology spectrum
|September 21, 2023
概括
现有的抗寄生虫药物尼弗拉泰尔有效向巨细胞内的细胞内沙门氏菌. 这种抗生素在治疗小鼠的沙门氏菌感染和对抗各种细菌病原体方面表现有前途.
科学领域:
- 微生物学 微生物学
- 传染性疾病 传染性疾病
- 药物发现 药物发现 药物发现
背景情况:
- 沙门氏菌中的抗生素耐药性,一个Enterobacteriaceae家族的成员,是一个日益增长的全球健康问题.
- 有效的治疗方法必须穿透宿主巨细胞,以对抗在含沙门氏菌的真空中存在的细胞内沙门氏菌.
- 沙门氏菌在巨细胞内持久的能力对完全清除宿主构成挑战,并可能导致再感染.
研究的目的:
- 选食品和药物管理局 (FDA) 批准的药物对抗细胞内沙门氏菌的有效性.
- 确定一种安全有效的抗生素,能够降低巨细胞内的细菌负载.
- 评估重新定位的药物治疗沙门氏菌感染的潜力.
主要方法:
- 在受感染的巨细胞中对FDA批准的药物小库进行查,以对抗快速繁殖的Salmonella Enteritidis突变体.
- 在巨细胞模型中评估药物疗效和细胞毒性.
- 用小鼠进行体内研究,以评估保护和减少细菌负载.
- 对各种沙门氏菌血清体进行检测,包括多抗药菌株,以及其他细菌病原体,如Listeria monocytogenes和Shigella flexneri.
主要成果:
- 尼弗拉泰尔是一种酸盐抗生素,表现出显著的抗菌活性和对巨细胞的低毒性.
- 在体内研究表明,尼弗拉泰尔在小鼠中提供了60%的保护,防止致命的沙门氏菌肠杆菌剂量,降低了组织中的细菌数量.
- 尼弗拉泰尔对各种沙门氏菌血清菌,多药耐药菌株和其他细胞内病原体,包括李斯特菌和西格拉菌有效.
- 该药物降低了受感染巨细胞中介质素-10 (IL-10) 和STAT3的产生,可能会增强宿主炎症反应.
结论:
- 尼弗拉泰尔是治疗沙门氏菌感染的有希望的候选者,因为它对细胞内细菌的有效性及其安全性.
- 重新利用尼弗拉泰尔提供了一种潜在的策略,可以对抗抗生素耐药的沙门氏菌菌株,并防止内源性再感染.
- 对尼弗拉泰尔的机制和临床应用的进一步研究对于感染性疾病的治疗是有必要的.
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