title: Lysine trimethylation of EF-Tu mimics platelet-activating factor to initiate Pseudomonas aeruginosa pneumonia.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors: Instituto Universitario de Investigación en Ciencias de la Salud, Universidad de las Islas Baleares, Palma de Mallorca, Spain.
authors: Mariette
authors: M
authors: Barbier
authors: Joshua P
authors: JP
authors: Owings
authors: Inmaculada
authors: I
authors: Martínez-Ramos
authors: F Heath
authors: FH
authors: Damron
authors: Rosa
authors: R
authors: Gomila
authors: Jesús
authors: J
authors: Blázquez
authors: Joanna B
authors: JB
authors: Goldberg
authors: Sebastián
authors: S
authors: Albertí
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism; D000818:Animals; D001422:Bacterial Adhesion; D005260:Female; D008239:Lysine / Q000378:metabolism*; D008297:Male; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010444:Peptide Elongation Factor Tu / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000378:metabolism*; D018410:Pneumonia, Bacterial / Q000382:microbiology*; D011499:Protein Processing, Post-Translational; D011550:Pseudomonas aeruginosa / Q000201:enzymology / Q000472:pathogenicity*; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D018829:Adhesins, Bacterial; D010972:Platelet Activating Factor; D037521:Virulence Factors; D008780:Methyltransferases; D010444:Peptide Elongation Factor Tu; D008239:Lysine
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