一种潜在的非传统方法来对抗
Xiaoming Wang1,2, Ting Liu1, Xi Lv1
1MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Antimicrobial agents and chemotherapy
|June 8, 2023
概括
黑色素通过破坏排泄来提高tigecycline对抗耐药Klebsiella肺炎的有效性. 这种组合疗法在治疗携带TMexCD1-TOprJ1基因的细菌引起的感染方面表现有前途.
科学领域:
- 微生物学 微生物学
- 药理学 药理学是指药理学的学科.
- 传染性疾病 传染性疾病
背景情况:
- 转移性耐药结节分裂 (RND) 型排泄的出现,如TMexCD1-TOprJ1,构成了严重的全球健康威胁,对tigecycline等关键抗生素产生耐药性.
- 含有TMexCD1-TOprJ1排泄的Klebsiella pneumoniae菌株对tigecycline的敏感性降低,使感染的治疗选择复杂化.
研究的目的:
- 为了研究黑激素与tigecycline结合对携带TMexCD1-TOprJ1排泄的Klebsiella pneumoniae菌株的潜在协同作用.
- 阐明黑色素增强tigecycline抗菌活性的潜在机制.
主要方法:
- 在体外敏感性测试以评估黑激素和tigecycline的协同抗菌活性.
- 对tigecycline在细菌细胞内积累的评估.
- 细菌细胞膜完整性和细胞内容泄漏的分析.
- 使用小鼠大腿感染模型进行体内验证.
主要成果:
- 黑色素显示出协同作用,显著增强了tigecycline对TMexCD1-TOprJ1阳性Klebsiella pneumoniae的抗菌疗效.
- 这种组合破坏了质子驱动力和排泄功能,导致tigecycline细胞内积累增加.
- 细菌细胞膜完整性的损伤和随后的细胞内容的泄漏被观察到.
- 在小鼠大腿感染模型中证实了协同效应,显示了治疗结果的改善.
结论:
- 黑色素与tigecycline协同作用,以克服Klebsiella pneumoniae中的TMexCD1-TOprJ1介导的耐药性.
- 组合疗法通过增加药物积累和损害细菌细胞完整性来增强tigecycline的疗效.
- 黑激素/提格环素组合是一种有前途的治疗策略,用于对抗携带TMexCD1-TOprJ1基因的多药耐药细菌引起的感染.
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