Pseudomonas aeruginosa potentiates the lethal effect of intestinal ischemia-reperfusion injury: the role of in vivo virulence activation.
Pseudomonas aeruginosa potentiates the lethal effect of intestinal ischemia-reperfusion injury: the role of in vivo virulence activation.
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铜绿假单胞菌增强肠道缺血再灌注损伤的致死效应：体内毒力激活的作用。
DOI：
10.1097/ta.0b013e31821cb7e5
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发表时间：
2011-12
期刊：
影响因子：
--
通讯作者：
Alverdy JC
中科院分区：
文献类型：
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作者：
Fink D;Romanowski K;Valuckaite V;Babrowski T;Kim M;Matthews JB;Liu D;Zaborina O;Alverdy JC
肠缺血再灌注（IR）损伤的实验模型总是在具有其正常肠道植物群的小鼠中进行，即使当人类被高致病性医院植物群定殖时，在长期重症监护禁闭期间在人类中发生多个肠IR事件。本研究的目的是确定远端肠道中人类病原体铜绿假单胞菌的存在是否增强了暴露于肠道IR的小鼠的致死率，并确定体内毒力激活在观察到的死亡率中的作用。7-9将一周大的C57/BL 6小鼠暴露于上级肠系膜动脉闭塞（SMAO）15分钟，随后将1.0 × 106 CFU的铜绿假单胞菌PAO 1直接肠内接种到回肠中，并观察死亡率。在单独的小鼠组中进行重复研究，以使用组成型生物发光铜绿假单胞菌PAO 1衍生物XEN 41和PAO 1的诱导型报道衍生物（条件性表达群体感应依赖性上皮毒力破坏蛋白PA-IL的PAO 1/lecA luxCDABE）的实时光子照相机成像来评估经阴道接种的菌株的迁移/播散模式和体内毒力激活。暴露于15分钟的SMAO和再灌注的肠接种铜绿假单胞菌的小鼠具有100%的显著增加的死亡率（p<0.001），相比之下，假手术小鼠经肠接种铜绿假单胞菌而无SMAO和仅肠IR的死亡率<10%（<50%）。铜绿假单胞菌在肠IR小鼠中的迁移/播散模式表明远端注射菌株向近端迁移，并易位至肠系膜淋巴结、肝、脾、肺和肾。建立了肠IR期间屏障破坏粘附素PA-IL的体内毒力表达的关键作用，因为其表达在IR期间增强，并且缺乏PA-IL的突变株显示出减弱的死亡率。肠道铜绿假单胞菌的存在增强了小鼠肠道IR的致死作用，部分原因是其上皮屏障破坏蛋白PA-IL的体内毒力激活。
Experimental models of intestinal ischemia reperfusion (IR) injury are invariably performed in mice harboring their normal commensal flora, even though multiple intestinal IR events occur in humans during prolonged intensive care confinement when they are colonized by a highly pathogenic hospital flora. The aims of this study were to determine if the presence of the human pathogen P. aeruginosa in the distal intestine potentiates the lethality of mice exposed to intestinal IR and to determine what role if any in vivo virulence activation plays in the observed mortality. 7-9 week old C57/BL6 mice were exposed to 15 minutes of superior mesenteric artery occlusion (SMAO) followed by direct intestinal inoculation of 1.0 × 106 CFU of P. aeruginosa PAO1 into the ileum and observed for mortality. Reiterative studies were performed in separate groups of mice to evaluate both the migration/dissemination pattern and in vivo virulence activation of intestinally inoculated strains using live photon camera imaging of both a constitutive bioluminescent P. aeruginosa PAO1 derivative XEN41 and an inducible reporter derivative of PAO1, the PAO1/lecA∷luxCDABE that conditionally expresses the quorum sensing dependent epithelial disrupting virulence protein PA-IL. Mice exposed to 15 minutes of SMAO and reperfusion with intestinal inoculation of P. aeruginosa had a significantly increased mortality rate (p<0.001) of 100% compared to <10% for sham operated mice intestinally inoculated with P. aeruginosa without SMAO and intestinal IR alone (<50%). Migration/dissemination patterns of P. aeruginosa in mice subjected to intestinal IR demonstrated proximal migration of distally injected strains and translocation to mesenteric lymph nodes, liver, spleen, lung, and kidney. A key role for in vivo virulence expression of the barrier disrupting adhesin PA-IL during intestinal IR was established since its expression was enhanced during IR and mutant strains lacking PA-IL displayed attenuated mortality. The presence of intestinal P. aeruginosa potentiates the lethal effect of intestinal IR in mice in part due to in vivo virulence activation of its epithelial barrier disrupting protein PA-IL.