Brucella, nitrogen and virulence

Abstract

The brucellae are α-Proteobacteria causing brucellosis, an important zoonosis. Although multiplying in endoplasmic reticulum-derived vacuoles, they cause no cell death, suggesting subtle but efficient use of host resources. Brucellae are amino-acid prototrophs able to grow with ammonium or use glutamate as the sole carbon-nitrogen source in vitro. They contain more than twice amino acid/peptide/polyamine uptake genes than the amino-acid auxotroph Legionella pneumophila, which multiplies in a similar vacuole, suggesting a different nutritional strategy. During these two last decades, many mutants of key actors in nitrogen metabolism (transporters, enzymes, regulators, etc.) have been described to be essential for full virulence of brucellae. Here, we review the genomic and experimental data on Brucella nitrogen metabolism and its connection with virulence. An analysis of various aspects of this metabolism (transport, assimilation, biosynthesis, catabolism, respiration and regulation) has highlighted differences and similarities in nitrogen metabolism with other α-Proteobacteria. Together, these data suggest that, during their intracellular life cycle, the brucellae use various nitrogen sources for biosynthesis, catabolism and respiration following a strategy that requires prototrophy and a tight regulation of nitrogen use.

Brucella Genital Tropism: What's on the Menu

“…Even though this is not true for all B. suis strains and at least some B. abortus and B. melitensis strains are respectively auxotrophic for specific amino acids or require a CO 2 supply for growing on glutamate (Plommet, 1991), the fact stands that all Brucella species have in common a remarkable capacity to oxidize exogenous glutamate (Verger and Grayon, 1977; Jacques et al, 2007). As expected, genomic and mutant analysis show that the brucellae keep a conventional enzymatic machinery for using glutamate both for amino acid synthesis and as a C source feeding the Krebs cycle (Ronneau et al, 2014). …”

RegA Plays a Key Role in Oxygen-Dependent Establishment of Persistence and in Isocitrate Lyase Activity, a Critical Determinant of In vivo Brucella suis Pathogenicity

“…RegA induced BR1118 ( ntrB ) and BR1119 ( nifR3 ) (Figure 3) of the ntrBC operon, encoding the two-component system involved in regulation of nitrogen metabolism and depending on glutamine availability (Ronneau et al, 2016). Since the downstream operon ntrYX is also regulated by PrrA (RegA) in B. abortus (Carrica et al, 2013), we compared ntrY (BR1116) expression levels in the WT and Δ regA strains by RT-qPCR.…”

Proline utilization system is required for infection by the pathogenic α-proteobacterium Brucella abortus

“…Furthermore, it is presumed that the brucellae possess de novo biosynthetic pathways for the 20 standard proteinogenic amino acids. Disruption of several different amino acid metabolic pathways and transport systems results in the attenuation of B. abortus, Brucella melitensis and Brucella suis in cellular and animal models of infection [10]. In addition, a number of genes linked to nitrogen utilization, including glnA, glnD and nrII, are essential for virulent infection, leading to the suggestion that there is a relative paucity of nitrogen and carbon sources available in the BCV, and that efficient use of resources is necessary for Brucella to colonize the host [11].…”