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柏巴胺通过调节ROS/Ca2+轴促进巨细胞的自,以清除Mycobacterium结核病

Su Zhang¹, Xuefeng Zhou², Min Ou¹

¹National Clinical Research Center for Infectious Diseases, Guangdong Provincial Clinical Research Center for Tuberculosis, Shenzhen Third People's Hospital, Southern University of Science and Technology , Shenzhen, China.

|June 29, 2023

概括

柏巴胺 (BBM) 通过通过ROS/Ca2+通路增强巨细胞自,有效清除耐药结核病 (TB). 这种FDA批准的药物显示出作为结核病治疗的宿主导疗法 (HDT) 的前景.

科学领域:

微生物学微生物学
免疫学免疫学免疫学
药理学药理学是指药理学的学科.

背景情况:

耐药结核病 (TB) 是全球卫生面临的重大挑战,需要新的治疗策略.
主体导向疗法 (HDT) 是一种新兴的方法,特别是用于对抗耐药结核病,通常涉及药物的重新用途.

研究的目的:

调查贝巴胺 (BBM) 的疗效,一个已知的类化合物,作为宿主导治疗细胞内Mycobacterium结核病 (Mtb) 在巨细胞内.
阐明BBM抗菌菌活动的潜在分子机制,重点关注自,活性氧物种 (ROS) 和 (Ca2+) 信号传递.

主要方法:

巨被Mtb感染,并评估了BBM对细胞内细菌生长,自标志物 (例如ATG5),ROS产生和Ca2+水平的影响.
药物抑制剂和抗氧化剂,如N-乙-L-氨酸 (NAC) 和BAPTA-AM,用于剖析涉及的信号通路.
评估了BBM对药物敏感和耐药Mtb菌株的活性.

主要成果:

通过促进自,BBM显著抑制了细胞内Mtb的生长,这种效应部分依赖ATG5.5.
BBM治疗增加了细胞内ROS水平,这对于诱导自和抑制Mtb存活至关重要,NAC治疗证明了这一点.
观察到ROS介导的Ca2+增加,并且通过BAPTA-AM阻断Ca2+信号,损害了BBM诱导自和清除Mtb的能力.
BBM证明了对抗耐药Mtb菌株的有效性.

结论:

柏巴胺 (BBM) 通过通过ROS/Ca2+信号轴调节巨细胞自,有效清除对药物敏感和耐药的Mtb.
作为FDA批准的药物,BBM作为结核病的宿主导治疗候选药物具有显著的潜力,可能改善治疗结果或缩短治疗时间.

关键词:

结核病菌菌菌的结核病菌的结核病菌.这就是ROSOS ROS.自自是自的过程.柏胺是一种胺.和是最重要的.

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