生物谷報道:美國加州大學(xué)研究人員在5月15日出版的《細(xì)胞-宿主與微生物》上發(fā)表了一篇有關(guān)結(jié)核分枝桿菌的最新研究報道,。
結(jié)核分枝桿菌表達(dá)體內(nèi)的被稱為休眠調(diào)節(jié)子一組基因,。這些基因在體外表達(dá)時可以響應(yīng)一氧化氮(NO)或組織缺氧,以及用于模擬結(jié)核分枝桿菌持續(xù)的潛伏感染,。雖然巨噬細(xì)胞的產(chǎn)物一氧化氮會抑制呼吸,,但缺氧卻有可能在體內(nèi)觸發(fā),,還可能激活感染期間的休眠調(diào)節(jié)子。
經(jīng)過研究表明,,結(jié)核分枝桿菌的感染刺激了巨噬細(xì)胞血紅素加氧酶(HO-1)的表達(dá),,這些酶的氣態(tài)產(chǎn)物——一氧化碳(CO)激活了休眠調(diào)節(jié)子的表達(dá)。巨噬細(xì)胞HO-1的清除可以降低休眠調(diào)節(jié)子的表達(dá),。此外研究表明,,結(jié)核分枝桿菌DosS/DosT/DosR的雙組分感應(yīng)器傳遞系統(tǒng)必需響應(yīng)CO。
總之,,這些研究結(jié)果顯示,,在巨噬細(xì)胞感染過程中結(jié)核分枝桿菌能夠感應(yīng)CO。CO也許代表了一個普遍的現(xiàn)象,,它提示我們使用的病原體感知和適應(yīng)宿主環(huán)境,。(生物谷www.bioon.com)
生物谷推薦原始出處:
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
[email protected]
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.