Global effects of the cell-to-cell signaling molecules autoinducer-2, autoinducer-3 an epinephrine in a luxS mutant of enterohemorrhagic Escherichia coli

Global effects of the cell-to-cell signaling molecules autoinducer-2, autoinducer-3 an epinephrine in a luxS mutant of enterohemorrhagic Escherichia coli
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DOI:
10.1128/iai.00550-07
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发表时间:
2007-10-01
影响因子:
3.1
通讯作者:
Sperandio, Vanessa
Sperandio, Vanessa
中科院分区:
医学2区
文献类型:
--
作者:
Kendall, Melissa M.;Rasko, David A.;Sperandio, Vanessa

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肠出血性大肠杆菌(EHEC)的界内细胞间通讯和界间细胞间通讯在其毒力中起重要作用。四种信号,自动诱导物2(AI-2),AI-3,以及人类激素肾上腺素和去甲肾上腺素,在这种通信中很重要。本研究检测了这些信号化合物对EHEC转录组的影响。我们证明了luxS突变主要影响致病性和非致病性大肠杆菌菌株的中心代谢基因。在缺乏合成AI-2能力的luxS缺陷型菌株中,添加外源AI-2不能完全恢复表达谱。添加AI-3或肾上腺素增加肠上皮细胞消退调节子位点的表达,已知其在EHEC毒力中起关键作用。此外,当肾上腺素添加到培养基中时,观察到最大数量的基因改变。这些改变包括在EHEC基因中的改变比在MG 1655基因中的改变更大的比例,这表明肾上腺素可能是全球毒力信号。用实时逆转录酶PCR(RT-PCR)进行的详细检查证实了加入AI-3和肾上腺素后毒力基因表达的增加。用实时RT-PCR检查EHEC分泌的效应物和推定的菌毛基因表达的额外研究显示可变的表达谱,表明分泌的分子存在差异调节。这项研究开始检查肠出血性大肠杆菌的全球信号网络,并揭示了信号和病原体特异性的表达谱。
Intrakingdom cell-to-cell communication and interkingdom cell-to-cell communication play essential roles in the virulence of enterohemorrhagic Escherichia coli (EHEC). Four signals, autoinducer 2 (AI-2), AI-3, and the human hormones epinephrine and norepinephrine, are important in this communication. The effect of these signaling compounds on the transcriptome of EHEC was examined in this study. We demonstrated that the luxS mutation affects primarily central metabolic genes in both pathogenic and nonpathogenic strains of E. coli and that addition of exogenous AI-2 does not fully restore the expression profile in a luxS-deficient strain lacking the ability to synthesize AI-2. Addition of AI-3 or epinephrine increased expression of the locus of enterocyte effacement regulon, which is known to play a pivotal role in EHEC virulence. Moreover, when epinephrine was added to the culture medium, the greatest number of gene alterations was observed. These alterations included a greater proportion of alterations in EHEC genes than in MG1655 genes, suggesting that epinephrine may be a global virulence signal. Detailed examination with real-time reverse transcriptase PCR (RT-PCR) confirmed the increases in virulence gene expression with addition of AI-3 and epinephrine. Additional studies with real-time RT-PCR examining the EHEC secreted effectors and putative fimbrial gene expression showed a variable expression profile, indicating that there is differential regulation of the secreted molecules. This study began to examine the global signaling networks in EHEC and revealed expression profiles that are signal and pathogen specific.