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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Autor principal: Valguarnera, E.
Otros Autores: 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: Capítulo de libro
Lenguaje:Inglés
Publicado: Oxford University Press 2018
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Acceso en línea:Registro en Scopus
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030 |a JIDIA 
100 1 |a Valguarnera, E. 
245 1 0 |a RomA, A Periplasmic Protein Involved in the Synthesis of the Lipopolysaccharide, Tunes Down the Inflammatory Response Triggered by Brucella 
260 |b Oxford University Press  |c 2018 
270 1 0 |m Ugalde, J.E.; Instituto de Investigaciones Biotecnológicas dr. Rodolfo A. Ugalde, IIB-INTECH, CONICET, Universidad Nacional de San Martín, Campus Miguelete, UNSAM, Avenida 25 de Mayo y Francia, Argentina; email: jugalde@iibintech.com.ar 
506 |2 openaire  |e Política editorial 
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504 |a Spera, J.M., Comerci, D.J., Ugalde, J.E., Brucella alters the immune response in a prpA-dependent manner (2014) Microb Pathog, 67-68, pp. 8-13 
504 |a Spera, J.M., Herrmann, C.K., Roset, M.S., Comerci, D.J., Ugalde, J.E., A Brucella virulence factor targets macrophages to trigger B-cell proliferation (2013) J Biol Chem, 288, pp. 20208-20216 
504 |a Spera, J.M., Ugalde, J.E., Mucci, J., Comerci, D.J., Ugalde, R.A., A B lymphocyte mitogen is a Brucella abortus virulence factor required for persistent infection (2006) Proc Natl Acad Sci USA, 103, pp. 16514-16519 
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504 |a Conde-Álvarez, R., Arce-Gorvel, V., Iriarte, M., The lipo-polysaccharide core of Brucella abortus acts as a shield against innate immunity recognition (2012) PLoS Pathog, 8, p. e1002675 
504 |a Döhmer, P.H., Valguarnera, E., Czibener, C., Ugalde, J.E., Identifcation of a type IV secretion substrate of Brucella abortus that participates in the early stages of intracellular survival (2014) Cell Microbiol, 16, pp. 396-410 
504 |a Roset, M.S., García Fernández, L., DelVecchio, V.G., Briones, G., Intracellularly induced cyclophilins play an important role in stress adaptation and virulence of Brucella abortus (2013) Infect Immun, 81, pp. 521-530 
504 |a Bligh, E.G., Dyer, W.J., A rapid method of total lipid extraction and purifcation (1959) Can J Biochem Physiol, 37, pp. 911-917 
504 |a White, P.G., Wilson, J.B., Diferentiation of smooth and nons-mooth colonies of Brucellae (1951) J Bacteriol, 61, pp. 239-240 
504 |a Luederitz, O., Risse, H.J., Schulte-Holthausen, H., Strominger, J.L., Sutherland, I.W., Westphal, O., Biochemical studies of the smooth-rough mutation in Salmonella Minnesota (1965) J Bacteriol, 89, pp. 343-354 
504 |a Ugalde, J.E., Czibener, C., Feldman, M.F., Ugalde, R.A., Identifcation and characterization of the Brucella abortus phosphoglucomutase gene: Role of lipopolysaccharide in virulence and intracellular multiplication (2000) Infect Immun, 68, pp. 5716-5723 
504 |a Ugalde, J.E., Comerci, D.J., Leguizamón, M.S., Ugalde, R.A., Evaluation of Brucella abortus phosphoglucomutase (pgm) mutant as a new live rough-phenotype vaccine (2003) Infect Immun, 71, pp. 6264-6269 
504 |a Guidolin, L.S., Morrone Seijo, S.M., Guaimas, F.F., Comerci, D.J., Ciocchini, A.E., Interaction network and localization of Brucella abortus membrane proteins involved in the synthesis, transport, and succinylation of cyclic β-1, 2-glucans (2015) J Bacteriol, 197, pp. 1640-1648 
504 |a Marchesini, M.I., Ugalde, J.E., Czibener, C., Comerci, D.J., Ugalde, R.A., N-terminal-capturing screening system for the isolation of Brucella abortus genes encoding surface exposed and secreted proteins (2004) Microb Pathog, 37, pp. 95-105 
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504 |a Dinh, T., Bernhardt, T.G., Using superfolder green fuores-cent protein for periplasmic protein localization studies (2011) J Bacteriol, 193, pp. 4984-4987 
504 |a West, N.P., Sansonetti, P., Mounier, J., Optimization of virulence functions through glucosylation of Shigella LPS (2005) Science, 307, pp. 1313-1317 
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520 3 |a 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).  |l eng 
536 |a Detalles de la financiación: National Council for Scientific Research 
536 |a Detalles de la financiación: Consejo Nacional de Investigaciones Científicas y Técnicas 
536 |a Detalles de la financiación: Acknowledgments. We thank members of the J.E.U. laboratory for useful discussions and Thomas Bernhardt from Harvard University for kindly providing the superfolder GFP coding plasmid. C. C., S. G. A., A. S. C., K. A. P., J. M. S., J. C. and J. E. U. are members of the National Research Council of Argentina (CONICET).  Financial support. This work was supported by grants PICT-PRH08-160 to C. C., PICT-PRH08-230 and PICT-1028-2014 to J. E. U., and grants from the University of San Martín to C. C. and J. E. U. E.V. was supported by a fellowship of the National Research Council of Argentina (CONICET). 
593 |a Instituto de Investigaciones Biotecnológicas dr. Rodolfo A. Ugalde, IIB-INTECH, CONICET, Universidad Nacional de San Martín, Campus Miguelete, UNSAM, Avenida 25 de Mayo y Francia, San Martín (1650), Buenos Aires, Argentina 
593 |a Facultad de Ciencias Exactas y Naturales, Departamento de Quimica Organica-Consejo Nacional de Lnvestigaciones Cientificas y Tecnicas, Centro de Investigación en Hidratos de Carbono (CIHIDECAR), Universidad de Buenos Aires, Buenos Aires, Argentina 
593 |a Instituto de Biología Molecular y Celular de Rosario (IBR), Departamento de Microbiología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Santa Fe, Argentina 
690 1 0 |a BRUCELLA 
690 1 0 |a INFLAMMATION 
690 1 0 |a LIPOPOLYSACCHARIDE 
690 1 0 |a LIPOPOLYSACCHARIDE 
690 1 0 |a PERIPLASMIC PROTEIN 
690 1 0 |a ROMA PROTEIN 
690 1 0 |a UNCLASSIFIED DRUG 
690 1 0 |a ALPHAPROTEOBACTERIA 
690 1 0 |a ANIMAL EXPERIMENT 
690 1 0 |a ANIMAL MODEL 
690 1 0 |a ARTICLE 
690 1 0 |a BACTERIAL GENE 
690 1 0 |a BACTERIAL OUTER MEMBRANE 
690 1 0 |a BACTERIAL STRAIN 
690 1 0 |a BACTERIAL VIRULENCE 
690 1 0 |a BACTERIUM ADHERENCE 
690 1 0 |a BIOSYNTHESIS 
690 1 0 |a BRUCELLA ABORTUS 
690 1 0 |a BRUCELLOSIS 
690 1 0 |a CARBOHYDRATE ANALYSIS 
690 1 0 |a CARBOHYDRATE SYNTHESIS 
690 1 0 |a CONTROLLED STUDY 
690 1 0 |a INFLAMMATION 
690 1 0 |a MACROMOLECULE 
690 1 0 |a MEMBRANE DAMAGE 
690 1 0 |a MOUSE 
690 1 0 |a MUTANT 
690 1 0 |a NONHUMAN 
690 1 0 |a PERIPLASM 
690 1 0 |a PHENOTYPE 
690 1 0 |a PRIORITY JOURNAL 
690 1 0 |a PROTEIN CARBOHYDRATE INTERACTION 
690 1 0 |a PROTEIN DETERMINATION 
690 1 0 |a PROTEIN FUNCTION 
650 1 7 |2 spines  |a HOMEOSTASIS 
700 1 |a Spera, J.M. 
700 1 |a Czibener, C. 
700 1 |a Fulgenzi, F.R. 
700 1 |a Casabuono, A.C. 
700 1 |a Altabe, S.G. 
700 1 |a Pasquevich, K.A. 
700 1 |a Guaimas, F. 
700 1 |a Cassataro, J. 
700 1 |a Couto, A.S. 
700 1 |a Ugalde, J.E. 
773 0 |d Oxford University Press, 2018  |g v. 217  |h pp. 1257-1266  |k n. 8  |p J. Infect. Dis.  |x 00221899  |w (AR-BaUEN)CENRE-5621  |t Journal of Infectious Diseases 
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