Differential regulation of the genes involved in riboflavin biosynthesis in Brucella abortus

GARCÍA-ANGULO, V. A., SERER, M. I., BONOMI, H. R. AND GOLDBAUM F.A.

CENPAT, Puerto Madryn, Argentina

Congreso; XLVI Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2010

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Brucellosis is a worldwide zoonosis caused by closely related intracellular Brucella spp that affects livestock and humans. These species conserve an atypical riboflavin pathway, that presents the ribH1 and ribH2 genes, which encode enzymes with 6,7-dimethyl-8-ribityllumazine synthase activity, that synthesizes a riboflavin precursor. In B. abortus, ribH2 is encoded in the chromosome II, contains an RFN riboswitch element in its 5’ region, is expressed during the intracellular phase and is required for the virulence in mice; while ribH1 is encoded in chromosome I and is dispensable for intracellular survival. These data suggest differences in the regulatory pathways for the ribH genes. In this work, we demonstrate that ribH2 is specifically repressed by riboflavin and flavin mononucleotide. On the other hand, ribH1 is transcribed polycistronically together with the riboflavin biosynthesis genes ribD and ribE, and the putative regulators nrdR and nusB genes. Overexpression of nusB produces a significative increase in the expression of ribH1, but not of ribH2. These results indicate the existence of two independent regulatory mechanisms for the ribH genes, probably acting at different stages of B. abortus life cycle.