两个组成系统的激活剂控制细胞分离和内在耐药性在Mycobacterium结核病
Liam D McDonough1, Shuqi Li2, Vanisha Munsamy-Govender2
1Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510.
概括
研究人员确定TapaA是菌根菌细胞生长的关键调节者,对于协调分裂和新极形成至关重要. 丢失Tapa会破坏生长,增加对结核病抗生素的敏感性,突出显示Tapa是潜在的药物标.
科学领域:
- 微生物学 微生物学
- 细胞生物学 细胞生物学
- 药物发现 药物发现 药物发现
背景情况:
- 菌根菌表现出独特的极性生长模式,与棒状细菌不同.
- 细胞分裂和新极点启动之间的精确协调对于菌根菌的生存至关重要.
- 了解这些机制为结核病和其他真菌细菌感染提供了潜在的药物点.
研究的目的:
- 确定调控细胞分裂和菌根菌中新极生长之间的过渡的关键调节者.
- 调查Tapa在菌根细胞循环进展和外重塑中的作用.
- 评估TapA作为潜在的治疗点,用于真菌细菌感染.
主要方法:
- 基因操纵,为Tapa.A.创造功能丧失突变体.
- 显微镜技术观察细胞分裂和极形成.
- 对抗生素敏感性测试,以评估TapA对抗药性影响.
主要成果:
- TapA被确定为从分裂过渡到新的极子生长的关键调节者.
- 在隔膜上,TapA与MtrB相互作用,启动皮糖甘酸酶表达的信号级联.
- TapA的损失导致分裂中断,异常极形成,以及对结核病抗生素敏感性增加.
结论:
- 塔帕是一种关键的调节器,将细胞周期进展,包膜重塑和真菌细菌的内在抗生素耐药性联系起来.
- 向TapA代表了开发新的抗结核疗法的一个有前途的战略.
- 对TapA介导途径的进一步研究可能会发现针对真菌菌病的新型药物标.
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