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Ramesh Rijal¹, Richard H Gomer¹

¹Gomer Lab, Department of Biology, Texas A&M University, College Station, TX, United States.

Frontiers in microbiology

|May 1, 2024

概括

结核菌 (Mtb) 使用多酸盐 (polyP) 耐受抗生素. 抑制聚P合成与氨酸与异化物协同作用,用于治疗结核病.

科学领域:

微生物学微生物学
分子生物学分子生物学
药物发现药物发现药物发现

背景情况:

结核病 (TB) 治疗具有挑战性,原因是Mycobacterium tuberculosis (Mtb) 的耐药性.
在Mtb中聚酸盐 (polyP) 积累增强了抗生素耐受性,在尼塞利亚淋病中,它增强了抗菌素耐药性.
细菌通过PolyP适应抗微生物压力的机制尚未完全理解.

研究的目的:

调查聚酸盐 (polyP) 在Mycobacterium结核病 (Mtb) 适应异化 (INH) 的作用.
评估氨酸的潜力,一个多酸盐激酶抑制剂,在对MTB的联合治疗中.

主要方法:

在暴露于INH的Mtb中监测聚P水平 (细胞,细胞外,细胞表面).
评估蛋白对INH诱导的聚聚积的作用.
评估氨酸和INH对MTB生长的协同效应在体外和在人类巨细胞内.
通过代谢学分析INH和蛋白对Mtb细胞包膜形成和代谢物水平的影响.

主要成果:

在对INH的反应中,mtb增强了多聚的积累 (细胞,细胞外,细胞表面).
氨酸抑制INH诱导的细胞外和细胞表面P.P.的增加.
氨酸和INH具有协同作用,在体外和巨细胞中减少了Mtb的生长.
结合INH和蛋白治疗抑制了Mtb细胞包膜的形成,并显著改变了代谢物水平,特别是那些参与细胞包膜合成的代谢物.

结论:

Mtb利用polyP积累作为一种适应机制,以耐受异化.
氨酸有效地阻断了这种由PolyP介导的适应.
加莱因和INH的组合显示出对Mtb的协同效果,这表明结核病治疗的有前途的治疗策略.

关键词:

结核病菌菌菌的结核病菌的结核病菌.抗生素耐受性耐受性盖尔·盖莱因 (Galein Gallein) 是一个美丽的城市.异化是一种异化.代谢生物组的代谢生物组聚酸聚酸盐是一种多酸盐.

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