生物谷报道:美国加州大学研究人员在5月15日出版的《细胞-宿主与微生物》上发表了一篇有关结核分枝杆菌的最新研究报道。
结核分枝杆菌表达体内的被称为休眠调节子一组基因。这些基因在体外表达时可以响应一氧化氮(NO)或组织缺氧,以及用于模拟结核分枝杆菌持续的潜伏感染。虽然巨噬细胞的产物一氧化氮会抑制呼吸,但缺氧却有可能在体内触发,还可能激活感染期间的休眠调节子。
经过研究表明,结核分枝杆菌的感染刺激了巨噬细胞血红素加氧酶(HO-1)的表达,这些酶的气态产物——一氧化碳(CO)激活了休眠调节子的表达。巨噬细胞HO-1的清除可以降低休眠调节子的表达。此外研究表明,结核分枝杆菌DosS/DosT/DosR的双组分感应器传递系统必需响应CO。
总之,这些研究结果显示,在巨噬细胞感染过程中结核分枝杆菌能够感应CO。CO也许代表了一个普遍的现象,它提示我们使用的病原体感知和适应宿主环境。(生物谷www.bioon.com)
生物谷推荐原始出处:
Cell Host & Microbe,Vol 3, 323-330, 15 May 2008,Michael U. Shiloh, Jeffery S. Cox
Mycobacterium tuberculosis Senses Host-Derived Carbon Monoxide during Macrophage Infection
Michael U. Shiloh,1,2,3 Paolo Manzanillo,2,3 and Jeffery S. Cox2,3,
1 Department of Medicine, Division of Infectious Diseases, University of California, San Francisco, San Francisco, CA 94158, USA
2 Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA
3 Program in Microbial Pathogenesis and Host Defense, University of California, San Francisco, San Francisco, CA 94158, USA
Corresponding author
Jeffery S. Cox
jeffery.cox@ucsf.edu
Summary
Mycobacterium tuberculosis (MTB) expresses a set of genes known as the dormancy regulon in vivo. These genes are expressed in vitro in response to nitric oxide (NO) or hypoxia, conditions used to model MTB persistence in latent infection. Although NO, a macrophage product that inhibits respiration, and hypoxia are likely triggers in vivo, additional cues could activate the dormancy regulon during infection. Here, we show that MTB infection stimulates expression of heme oxygenase (HO-1) by macrophages and that the gaseous product of this enzyme, carbon monoxide (CO), activates expression of the dormancy regulon. Deletion of macrophage HO-1 reduced expression of the dormancy regulon. Furthermore, we show that the MTB DosS/DosT/DosR two-component sensory relay system is required for the response to CO. Together, these findings demonstrate that MTB senses CO during macrophage infection. CO may represent a general cue used by pathogens to sense and adapt to the host environment.