RomA, A Periplasmic Protein Involved in the Synthesis of the Lipopolysaccharide, Tunes Down the Inflammatory Response Triggered by Brucella

Brucellaceae are stealthy pathogens with the ability to survive and replicate in the host in the context of a strong immune response. This capacity relies on several virulence factors that are able to modulate the immune system and in their structural components that have low proinflammatory activit...

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Detalles Bibliográficos
Autores principales: Valguarnera, E., Spera, J.M., Czibener, C., Fulgenzi, F.R., Casabuono, A.C., Altabe, S.G., Pasquevich, K.A., Guaimas, F., Cassataro, J., Couto, A.S., Ugalde, J.E.
Formato: JOUR
Materias:
Brucella
inflammation
lipopolysaccharide
periplasmic protein
RomA protein
unclassified drug
Alphaproteobacteria
animal experiment
animal model
Article
bacterial gene
bacterial outer membrane
bacterial strain
bacterial virulence
bacterium adherence
biosynthesis
Brucella abortus
brucellosis
carbohydrate analysis
carbohydrate synthesis
controlled study
homeostasis
macromolecule
membrane damage
mouse
mutant
nonhuman
periplasm
phenotype
priority journal
protein carbohydrate interaction
protein determination
protein function
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_00221899_v217_n8_p1257_Valguarnera
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario:Brucellaceae are stealthy pathogens with the ability to survive and replicate in the host in the context of a strong immune response. This capacity relies on several virulence factors that are able to modulate the immune system and in their structural components that have low proinflammatory activities. Lipopolysaccharide (LPS), the main component of the outer membrane, is a central virulence factor of Brucella, and it has been well established that it induces a low inflammatory response. We describe here the identification and characterization of a novel periplasmic protein (RomA) conserved in alpha-proteobacteria, which is involved in the homeostasis of the outer membrane. A mutant in this gene showed several phenotypes, such as membrane defects, altered LPS composition, reduced adhesion, and increased virulence and inflammation. We show that RomA is involved in the synthesis of LPS, probably coordinating part of the biosynthetic complex in the periplasm. Its absence alters the normal synthesis of this macromolecule and affects the homeostasis of the outer membrane, resulting in a strain with a hyperinflammatory phenotype. Our results suggest that the proper synthesis of LPS is central to maximize virulence and minimize inflammation. © 2017 The Author(s).

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