Lysine trimethylation of EF-Tu mimics platelet-activating factor to initiate Pseudomonas aeruginosa pneumonia.
Lysine trimethylation of EF-Tu mimics platelet-activating factor to initiate Pseudomonas aeruginosa pneumonia.
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DOI：
10.1128/mbio.00207-13
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发表时间：
2013-05-07
期刊：
影响因子：
6.4
通讯作者：
Albertí S
中科院分区：
文献类型：
--
作者：
Barbier M;Owings JP;Martínez-Ramos I;Damron FH;Gomila R;Blázquez J;Goldberg JB;Albertí S
铜绿假单胞菌是一种无处不在的微生物，是与医院肺炎相关的最常见的革兰氏阴性细菌，这是重症患者死亡的主要原因，尽管在这种病原体中却鲜为人知。为了在这里引发宿主的感染。未识别的细菌配体与铜绿假单胞菌有关早期宿主定植。 。这是在呼吸道感染的鼠模型中肺炎的先决条件。
从微生物和免疫学的角度来看，磷酸胆碱是一个有趣的分子工作在结构上鉴定出新型的细菌表面表位，并且在功能上与磷酸胆碱的功能相似。铜绿假单胞菌和肺炎的发育开发了新的药物的新靶标，以防止铜绿假单胞菌肺炎，鉴于经常紧急的多药抗性菌株，这尤其重要。
Pseudomonas aeruginosa is a ubiquitous microorganism and the most common Gram-negative bacterium associated with nosocomial pneumonia, which is a leading cause of mortality among critically ill patients. Although many virulence factors have been identified in this pathogen, little is known about the bacterial components required to initiate infection in the host. Here, we identified a unique trimethyl lysine posttranslational modification of elongation factor Tu as a previously unrecognized bacterial ligand involved in early host colonization by P. aeruginosa. This modification is carried out by a novel methyltransferase, here named elongation factor Tu-modifying enzyme, resulting in a motif that is a structural mimic of the phosphorylcholine present in platelet-activating factor. This novel motif mediates bacterial attachment to airway respiratory cells through platelet-activating factor receptor and is a major virulence factor, expression of which is a prerequisite to pneumonia in a murine model of respiratory infection. Phosphorylcholine is an interesting molecule from the microbiological and immunological point of view. It is a crucial epitope for the virulence of many important human pathogens, modulates the host immune response, and is involved in a wide number of processes ranging from allergy to inflammation. Our current work identifies a novel bacterial surface epitope structurally and functionally similar to phosphorylcholine. This novel epitope is crucial for initial colonization of the respiratory tract by Pseudomonas aeruginosa and for development of pneumonia. This opens up new targets for the development of novel drugs to prevent P. aeruginosa pneumonia, which is particularly important given the frequent emergence of multidrug-resistant strains.