The regulon of Brucella abortus two-component system BvrR/BvrS reveals the coordination of metabolic pathways required for intracellular life

• DOI: 10.1371/journal.pone.0274397
• Publication Date: 2022-09-21T17:32:39Z
• Authors: Olga Rivas-Solano; Mathilde Van der ...; Amanda Castillo-Z...; Marcela Suárez-Es...; Lohendy Muñoz-Vargas; Zeuz Capitan-Barrios; Nicholas R. Thomson; Esteban Chaves-Ol...; Edgardo Moreno; Xavier De Bolle; Caterina Guzmán-V...
• Keywords: Nitrogen; Science; CATTLE; Brucella abortus; ZOONOSIS; Regulon; Brucellosis; 03 medical and health sciences; Bacterial Proteins; Humans; BACTERIAS; BRUCELLOSIS; PATHOGENS; 0303 health sciences; Nucleotides; Q; ORGANISMOS PATÓGENOS; R; DNA; Gene Expression Regulation, Bacterial; Carbon; BRUCELOSIS; GANADO BOVINO; Medicine; Metabolic Networks and Pathways; Research Article

Brucella abortusis a facultative intracellular pathogen causing a severe zoonotic disease worldwide. The two-component regulatory system (TCS) BvrR/BvrS ofB.abortusis conserved in members of theAlphaproteobacteriaclass. It is related to the expression of genes required for host interaction and intracellular survival. Here we report thatbvrRandbvrSare part of an operon composed of 16 genes encoding functions related to nitrogen metabolism, DNA repair and recombination, cell cycle arrest, and stress response. Synteny of this genomic region within closeAlphaproteobacteriamembers suggests a conserved role in coordinating the expression of carbon and nitrogen metabolic pathways. In addition, we performed a ChIP-Seq analysis after exposure of bacteria to conditions that mimic the intracellular environment. Genes encoding enzymes at metabolic crossroads of the pentose phosphate shunt, gluconeogenesis, cell envelope homeostasis, nucleotide synthesis, cell division, and virulence are BvrR/BvrS direct targets. A 14 bp DNA BvrR binding motif was found and investigated in selected gene targets such asvirB1,bvrR,pckA,omp25, andtamA. Understanding gene expression regulation is essential to elucidate howBrucellaorchestrates a physiological response leading to a furtive pathogenic strategy.