结核分枝杆菌Lsr2是一个全球性的转录监管机构要求适应改变氧气浓度和毒性。
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Bartek, Woolhiser路,Baughn广告,Basaraba RJ,雅各布斯WR Jr Lenaerts AJ, Voskuil MI
结核分枝杆菌Lsr2是一个全球性的转录监管机构要求适应改变氧气浓度和毒性。
MBio。2014年6月3;5 (3):e01106-14。doi: 10.1128 / mBio.01106-14。
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24895305 (在PubMed]
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未标记的:动态主机环境中生存,结核分枝杆菌必须忍受一系列挑战,从活性氧和氮氧压力剧烈变化的可用性。分枝杆菌Lsr2蛋白已经与活性氧防御通过DNA的直接保护。检查Lsr2在发病机制中的作用和生理的结核分枝杆菌,我们生成一个应变Lsr2删除。分析结核分枝杆菌Deltalsr2应变表明,Lsr2 DNA不需要保护,这一毒株也同样敏感的野生型DNA有害。lsr2突变并显示严重的生长缺陷在常氧和氧的条件下,但它不是在低氧条件下生长所需。然而,它也适应乏氧生活所需。厌氧适应导致的缺陷显著减少在乏氧生活的可行性,以及复苏滞后。Deltalsr2突变体的基因表达分析在有氧和无氧条件下与DNA结合位点数据表明Lsr2发表是一个全球性的转录监管机构控制适应变化的氧含量。Deltalsr2应变是能够建立一个早期感染BALB / c小鼠模型;然而,它在坚持在肺部严重缺陷,没有造成明显的肺部病理。 These findings demonstrate M. tuberculosis Lsr2 is a global transcriptional regulator required for control of genes involved in adaptation to extremes in oxygen availability and is required for persistent infection. IMPORTANCE: M. tuberculosis causes nearly two million deaths per year and infects nearly one-third of the world population. The success of this aerobic pathogen is due in part to its ability to successfully adapt to constantly changing oxygen availability throughout the infectious cycle, from the high oxygen tension during aerosol transmission to anaerobiosis within necrotic lesions. An understanding of how M. tuberculosis copes with these changes in oxygen tension is critical for its eventual eradication. Using a mutation in lsr2, we demonstrate that the Lsr2 protein present in all mycobacteria is a global transcriptional regulator in control of genes required for adaptation to changes in oxygen levels. M. tuberculosis lacking lsr2 was unable to adapt to both high and very low levels of oxygen and was defective in long-term anaerobic survival. Lsr2 was also required for disease pathology and for chronic infection in a mouse model of TB.