RomA, a Periplasmic Protein Involved in the Synthesis of the Lipopolysaccharide Tunes Down the Inflammatory Response Triggered by Brucella.
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. and Ugalde, J.E.
Instituto de Investigaciones Biotecnologicas "Dr. Rodolfo A. Ugalde", IIB-INTECH, CONICET, Universidad Nacional de San Martin, San Martin, Buenos Aires, Argentina.
Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Quimica Organica - Consejo Nacional de lnvestigaciones Cientificas y Tecnicas. Centro de Investigacion en Hidratos de Carbono (CIHIDECAR). Buenos Aires, Argentina.
Instituto de Biologia Molecular y Celular de Rosario (IBR) and Departamento de Microbiologia, Facultad de Ciencias Bioquimicas y Farmaceuticas, Universidad Nacional de Rosario, Rosario, Santa Fe, Argentina.
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 pro-inflammatory activities. Lipopolysaccharide (LPS), the main component of the outer membrane, is a central virulence factor of Brucella and it has been well established that induces a low inflammatory response. We describe here the identification and characterization of a novel periplasmic protein (RomA) conserved in alpha-proteobacteria, 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 in order to maximize virulence and minimize inflammation.
The Journal of Infectious Diseases : en prensa (2018)