CodY regulation is required for full virulence and heme iron acquisition in Bacillus anthracis
CodY regulation is required for full virulence and heme iron acquisition in Bacillus anthracis
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DOI：
10.1096/fj.11-188912
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发表时间：
2011-12-01
期刊：
影响因子：
4.8
通讯作者：
Fouet, Agnes
中科院分区：
文献类型：
--
作者：
Chateau, Alice;van Schaik, Willem;Fouet, Agnes
荚膜和毒素是炭疽杆菌的主要毒力因子。B。炭疽菌多效性调节子CodY通过后诱导调节全局调节子AtxA的积累来激活毒素基因表达。然而，CodY对B.炭疽菌的包囊和包囊菌株的毒力是未知的。CodY在B.在小鼠和豚鼠模型中研究了炭疽菌的毒力。通过生物发光成像，在小鼠中追踪孢子生长和营养细胞的传播。我们还确定了封装状态和codY突变体生长所需的铁。在测试的所有模型中，codY突变株与野生型株相比被强烈减毒，并且在小鼠中，也与atxA株相比。codY的破坏不影响离体或体内封装，而atxA缺失只影响离体封装。codY的破坏导致延迟开始传播，但随后的细菌传播的动力学相似。codY突变体不能生长在血红素铁作为唯一的铁源，而亲本和补充菌株可以。缺乏CodY介导的转录通过控制铁的获得和毒素的合成来削弱毒力，但不改变封装。Chateau，A.，货车Schaik，W.，六号A Aucher，W.，Fouet，A. CodY调控是炭疽芽孢杆菌完全毒力和血红素铁获得所必需的。FASEB J. 25，4445-4456（2011）。www.fasebj.org
Capsule and toxin are the major virulence factors of Bacillus anthracis. The B. anthracis pleiotropic regulator CodY activates toxin gene expression by post-translationally regulating the accumulation of the global regulator AtxA. However, the role of CodY on B. anthracis capsulation and virulence of encapsulated strains has been unknown. The role of CodY in B. anthracis virulence was studied in mouse and guinea pig models. Spore outgrowth and dissemination of the vegetative cells was followed in mice by bioluminescent imaging. We also determined the state of capsulation and the iron requirement for growth of the codY mutant. In all models tested, the codY mutant strain was strongly attenuated compared to the wildtype strain and, in mice, also compared to the atxA strain. The disruption of codY did not affect either ex vivo or in vivo capsulation, whereas atxA deletion affected ex vivo capsulation only. The disruption of codY led to a delayed initiation of dissemination but similar kinetics of subsequent spread of the bacilli. The codY mutant cannot grow on heme iron as sole iron source, whereas the parental and complemented strains can. The lack of CodY-mediated transcription weakens virulence by controlling iron acquisition and synthesis of toxin, but without modifying capsulation.-Chateau, A., van Schaik, W., Six, A., Aucher, W., Fouet, A. CodY regulation is required for full virulence and heme iron acquisition in Bacillus anthracis. FASEB J. 25, 4445-4456 (2011). www.fasebj.org