Lysine Trimethylation of EF-Tu Mimics Platelet-Activating Factor To Initiate <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> 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...

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Autores principales:	Mariette Barbier, Joshua P. Owings, Inmaculada Martínez-Ramos, F. Heath Damron, Rosa Gomila, Jesús Blázquez, Joanna B. Goldberg, Sebastián Albertí
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2013
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/4c392d8e9d81476f9b77800637d16f90
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spelling	oai:doaj.org-article:4c392d8e9d81476f9b77800637d16f902021-11-15T15:40:06ZLysine Trimethylation of EF-Tu Mimics Platelet-Activating Factor To Initiate <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Pneumonia10.1128/mBio.00207-132150-7511https://doaj.org/article/4c392d8e9d81476f9b77800637d16f902013-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00207-13https://doaj.org/toc/2150-7511ABSTRACT 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. IMPORTANCE 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.Mariette BarbierJoshua P. OwingsInmaculada Martínez-RamosF. Heath DamronRosa GomilaJesús BlázquezJoanna B. GoldbergSebastián AlbertíAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 4, Iss 3 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Mariette Barbier Joshua P. Owings Inmaculada Martínez-Ramos F. Heath Damron Rosa Gomila Jesús Blázquez Joanna B. Goldberg Sebastián Albertí Lysine Trimethylation of EF-Tu Mimics Platelet-Activating Factor To Initiate <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Pneumonia
description	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. IMPORTANCE 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.
format	article
author	Mariette Barbier Joshua P. Owings Inmaculada Martínez-Ramos F. Heath Damron Rosa Gomila Jesús Blázquez Joanna B. Goldberg Sebastián Albertí
author_facet	Mariette Barbier Joshua P. Owings Inmaculada Martínez-Ramos F. Heath Damron Rosa Gomila Jesús Blázquez Joanna B. Goldberg Sebastián Albertí
author_sort	Mariette Barbier
title	Lysine Trimethylation of EF-Tu Mimics Platelet-Activating Factor To Initiate <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Pneumonia
title_short	Lysine Trimethylation of EF-Tu Mimics Platelet-Activating Factor To Initiate <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Pneumonia
title_full	Lysine Trimethylation of EF-Tu Mimics Platelet-Activating Factor To Initiate <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Pneumonia
title_fullStr	Lysine Trimethylation of EF-Tu Mimics Platelet-Activating Factor To Initiate <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Pneumonia
title_full_unstemmed	Lysine Trimethylation of EF-Tu Mimics Platelet-Activating Factor To Initiate <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Pneumonia
title_sort	lysine trimethylation of ef-tu mimics platelet-activating factor to initiate <named-content content-type="genus-species">pseudomonas aeruginosa</named-content> pneumonia
publisher	American Society for Microbiology
publishDate	2013
url	https://doaj.org/article/4c392d8e9d81476f9b77800637d16f90
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Lysine Trimethylation of EF-Tu Mimics Platelet-Activating Factor To Initiate <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Pneumonia

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