硫化氢刺激结核分枝杆菌呼吸、生长和发病的机制

Hydrogen sulfide stimulates Mycobacterium tuberculosis respiration, growth and pathogenesis

 

 

 

Keywords：Bacterial pathogenesis, Pathogens, Tuberculosis

关键词：细菌发病机制，病原体，结核病
作者：Saini V, Chinta KC, Reddy VP, Glasgow JN, Stein A, Lamprecht DA, Rahman MA, Mackenzie JS, Truebody BE, Adamson JH, Kunota TTR, Bailey SM, Moellering DR, Lancaster JR Jr, Steyn AJC
出版期刊：《Nature Communications》 2020/1/28

 

Abstract：

Hydrogen sulfide (H2S) is involved in numerous pathophysiological processes and shares overlapping functions with CO and •NO. However, the importance of host-derived H2S in microbial pathogenesis is unknown. Here we show that Mtb-infected mice deficient in the H2S-producing enzyme cystathionine β-synthase (CBS) survive longer with reduced organ
burden, and that pharmacological inhibition of CBS reduces Mtb bacillary load in mice. Highresolution respirometry, transcriptomics and mass spectrometry establish that H2S stimulates Mtb respiration and bioenergetics predominantly via cytochrome bd oxidase, and that H2S reverses •NO-mediated inhibition of Mtb respiration. Further, exposure of Mtb to H2S regulates genes involved in sulfur and copper metabolism and the Dos regulon. Our results indicate that Mtb exploits host-derived H2S to promote growth and disease, and suggest that host-directed therapies targeting H2S production may be potentially useful for the management of tuberculosis and other microbial infections.

 

文章摘要：

硫化氢 (H2S) 参与许多病理生理过程，并与 CO 和 •NO 具有重叠功能。然而，宿主衍生的 H2S 在微生物发病机制中的重要性尚不清楚。这里我们表明 Mtb 感染的小鼠缺乏 H2S-产生酶胱硫醚 β-合酶 (CBS) 存活时间更长，器官负担减少，CBS 的药理学抑制降低了小鼠的 Mtb 细菌负荷。高分辨率呼​​吸测定法、转录组学和质谱法确定 H2S 主要通过细胞色素 bd 氧化酶刺激 Mtb 呼吸和生物能量学，并且 H2S 逆转 •NO 介导的 Mtb 呼吸抑制。此外，Mtb 暴露于 H2S 可调节参与硫和铜代谢以及 Dos regulon 的基因。我们的结果表明 Mtb 利用宿主衍生的 H2S 促进生长和疾病，并且表明针对 H2S 产生的宿主导向疗法可能对结核病和其他微生物感染。

 

 

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