由Aureobasidin A引起的Candida spp临床耐药菌株的结构和功能变化
Rodrigo Rollin-Pinheiro1, Daniel Clemente de Moraes2, Brayan Bayona-Pacheco2,3
1Laboratório de Química Biológica de Microrganismos, Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil.
Journal of fungi (Basel, Switzerland)
|November 24, 2023
概括
奥里奥巴西丁A在对抗抗性Candida真菌感染方面表现有前途. 当与可纳结合时,它有效地向Candida生物膜,并保护动物模型免受感染.
科学领域:
- 菌类学 菌类学是指菌类学.
- 传染性疾病 传染性疾病
- 药理学 药理学是指药理学的学科.
背景情况:
- 由Candida物种引起的侵入性真菌感染是一个重大的全球健康问题.
- 在Candida分离物中,可纳耐药性需要探索替代性抗真菌剂.
- 脂生物合成是抗真菌药物开发的验证目标.
研究的目的:
- 为了研究 aureobasidin A 的疗效,一个脂蛋白生物合成抑制剂,对 Candida 生物膜和侵入性感染.
- 评估aureobasidin A与现有的抗真菌药物结合的协同作用潜力.
- 为了阐明奥雷巴西丁A抗真菌活性背后的细胞机制.
主要方法:
- 对Candida生物膜进行抗真菌敏感性测试.
- 在小鼠感染模型中的体内疗效研究.
- 对细胞损伤标记物的分析,包括氧化应激,膜潜力和DNA泄漏.
- 研究排泄抑制和细胞壁完整性的研究.
主要成果:
- 单独的奥利奥巴西丁A缺乏抗生素膜活性,并且与安福特素B没有协同作用.
- 青素A和可纳的组合显示出显著的抗菌膜疗效和体内保护.
- 细胞分析显示,在接受治疗的Candida中,氧化应激增加,线粒体潜力降低,细胞壁完整性受损.
- 奥里奥巴西丁A似乎抑制了CaCdr2p的排泄,并增加了对SDS的敏感性.
结论:
- 奥里奥巴西丁A,特别是与可纳结合使用,代表了对抗可纳耐药的Candida生物膜和感染的有前途的治疗策略.
- 该药物诱导了显著的细胞应激,并损害了Candida物种中的细胞完整性.
- 对黄素A的进一步研究有可能对抗具有挑战性的Candida感染进行临床应用.
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