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脆弱拟杆菌对氧气和过氧化氢的转录组反应:OxyR的作用及其对生存和毒力的影响。

The Bacteroides fragilis transcriptome response to oxygen and H2O2: the role of OxyR and its effect on survival and virulence.

作者信息

Sund Christian J, Rocha Edson R, Tzianabos Arthur O, Wells W Greg, Gee Jason M, Reott Michael A, O'Rourke Dorcas P, Smith C Jeffrey

机构信息

Department of Microbiology and Immunology, East Carolina University, Brody School of Medicine, Greenville, NC 27834, USA.

出版信息

Mol Microbiol. 2008 Jan;67(1):129-42. doi: 10.1111/j.1365-2958.2007.06031.x. Epub 2007 Nov 28.

DOI:10.1111/j.1365-2958.2007.06031.x
PMID:18047569
Abstract

The intestinal anaerobic symbiont, Bacteroides fragilis, is highly aerotolerant and resistant to H(2)O(2). Analysis of the transcriptome showed that expression of 45% of the genome was significantly affected by oxidative stress. The gene expression patterns suggested that exposure to oxidative stress induced an acute response to rapidly minimize the immediate effects of reactive oxygen species, then upon extended exposure a broad metabolic response was induced. This metabolic response induced genes encoding enzymes that can supply reducing power for detoxification and restore energy-generating capacity. An integral aspect of the metabolic response was downregulation of genes related to translation and biosynthesis which correlated with decreased growth and entry into a stationary phase-like growth state. Examination of oxyR mutants showed that they were impaired for the acute response and they induced the expanded metabolic response with only minimal exposure to stress. The oxyR mutants were more sensitive to oxidants in vitro and in vivo they were attenuated in an intra-abdominal abscess infection model. Aerotolerance and resistance to oxidative stress are physiological adaptations of B. fragilis to its environment that enhance survival in extra-intestinal sites and promote opportunistic infections.

摘要

肠道厌氧共生菌脆弱拟杆菌具有高度的耐氧性且对过氧化氢具有抗性。转录组分析表明,基因组中45%的基因表达受到氧化应激的显著影响。基因表达模式表明,暴露于氧化应激会引发急性反应,以迅速将活性氧的即时影响降至最低,然后在长时间暴露后会诱导广泛的代谢反应。这种代谢反应诱导了编码能够提供解毒所需还原力并恢复能量生成能力的酶的基因表达。代谢反应的一个重要方面是与翻译和生物合成相关的基因下调,这与生长减少和进入类似稳定期的生长状态相关。对oxyR突变体的研究表明,它们在急性反应中受损,并且仅在极少的应激暴露下就诱导了扩展的代谢反应。oxyR突变体在体外对氧化剂更敏感,在体内,它们在腹腔脓肿感染模型中毒力减弱。耐氧性和对氧化应激的抗性是脆弱拟杆菌对其环境的生理适应,可增强其在肠道外部位的生存能力并促进机会性感染。

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