TY - JOUR
T1 - The regulon of Brucella abortus two-component system BvrR/BvrS reveals the coordination of metabolic pathways required for intracellular life
AU - Rivas-Solano, Olga
AU - Van Der Henst, Mathilde
AU - Castillo-Zeledón, Amanda
AU - Suárez-Esquivel, Marcela
AU - Muñoz-Vargas, Lohendy
AU - Capitan-Barrios, Zeuz
AU - Thomson, Nicholas R.
AU - Chaves-Olarte, Esteban
AU - Moreno, Edgardo
AU - De Bolle, Xavier
AU - Guzmán-Verri, Caterina
N1 - Funding Information:
Fondos del Sistema FEES/CONARE [02-2020 to C.G-V], Fondos FIDA, Universidad Nacional [SIA 0047-17 to C. G-V], Espacio Universitario de Estudios Avanzados, UCREA [B8762 and C0456 to E.C-O] from the presidency of University of Costa Rica, the Vice Presidency for Research, University of Costa Rica. Instituto Tecnológico de Costa Rica (ITCR) [15-15-D to O.R-S], PINN-MICITT [PND-137-15-1 to O.R-S]. Fonds de la Recherche Scientifique-Fonds National de la Recherche Scientifique (F.R.S.-FNRS) [PDR Brucell-cycle T.0060.15 to X.D.B., FRIA Doctoral Grant to M.V.d. H.], and Wellcome Trust Sanger Institute [098051 to N.R.T]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Reynaldo Pereira-Reyes for his technical assistance with Dnase I footprinting and the purification of recombinant BvrR for EMSA experiments. We also thank Gustavo Segura-Umaña for his help with the interactive visualization of the genomic regions considered to be bound to BvrR under stress conditions.
Publisher Copyright:
© 2022 Rivas-Solano et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2022/9
Y1 - 2022/9
N2 - Brucella abortus is a facultative intracellular pathogen causing a severe zoonotic disease worldwide. The two-component regulatory system (TCS) BvrR/BvrS of B. abortus is conserved in members of the Alphaproteobacteria class. It is related to the expression of genes required for host interaction and intracellular survival. Here we report that bvrR and bvrS are 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 close Alphaproteobacteria members 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 as virB1, bvrR, pckA, omp25, and tamA. Understanding gene expression regulation is essential to elucidate how Brucella orchestrates a physiological response leading to a furtive pathogenic strategy.
AB - Brucella abortus is a facultative intracellular pathogen causing a severe zoonotic disease worldwide. The two-component regulatory system (TCS) BvrR/BvrS of B. abortus is conserved in members of the Alphaproteobacteria class. It is related to the expression of genes required for host interaction and intracellular survival. Here we report that bvrR and bvrS are 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 close Alphaproteobacteria members 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 as virB1, bvrR, pckA, omp25, and tamA. Understanding gene expression regulation is essential to elucidate how Brucella orchestrates a physiological response leading to a furtive pathogenic strategy.
UR - http://www.scopus.com/inward/record.url?scp=85138457779&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0274397
DO - 10.1371/journal.pone.0274397
M3 - Article
C2 - 36129877
AN - SCOPUS:85138457779
SN - 1932-6203
VL - 17
JO - PLoS ONE
JF - PLoS ONE
IS - 9 September
M1 - e0274397
ER -
