A Sinorhizobium meliloti and Agrobacterium tumefaciens ExoR ortholog is not crucial for Brucella abortus virulence

PLoS One. 2021 Aug 13;16(8):e0254568. doi: 10.1371/journal.pone.0254568. eCollection 2021.

Abstract

Brucella is a facultative extracellular-intracellular pathogen that belongs to the Alphaproteobacteria class. Precise sensing of environmental changes and a proper response mediated by a gene expression regulatory network are essential for this pathogen to survive. The plant-related Alphaproteobacteria Sinorhizobium meliloti and Agrobacterium tumefaciens also alternate from a free to a host-associated life, where a regulatory invasion switch is needed for this transition. This switch is composed of a two-component regulatory system (TCS) and a global inhibitor, ExoR. In B. abortus, the BvrR/BvrS TCS is essential for intracellular survival. However, the presence of a TCS inhibitor, such as ExoR, in Brucella is still unknown. In this work, we identified a genomic sequence similar to S. meliloti exoR in the B. abortus 2308W genome, constructed an exoR mutant strain, and performed its characterization through ex vivo and in vivo assays. Our findings indicate that ExoR is related to the BvrR phosphorylation state, and is related to the expression of known BvrR/BrvS gene targets, such as virB8, vjbR, and omp25 when grown in rich medium or starving conditions. Despite this, the exoR mutant strain showed no significant differences as compared to the wild-type strain, related to resistance to polymyxin B or human non-immune serum, intracellular replication, or infectivity in a mice model. ExoR in B. abortus is related to BvrR/BvrS as observed in other Rhizobiales; however, its function seems different from that observed for its orthologs described in A. tumefaciens and S. meliloti.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agrobacterium tumefaciens / drug effects
  • Agrobacterium tumefaciens / genetics*
  • Animals
  • Bacterial Proteins / genetics
  • Brucella abortus / genetics
  • Brucella abortus / pathogenicity*
  • Brucellosis / genetics
  • Brucellosis / microbiology
  • Brucellosis / pathology
  • Brucellosis / prevention & control*
  • Gene Expression Regulation, Bacterial / genetics
  • Host-Parasite Interactions / genetics
  • Humans
  • Mice
  • Mutation / genetics
  • Polymyxin B / pharmacology
  • Sinorhizobium meliloti / drug effects
  • Sinorhizobium meliloti / genetics*
  • Virulence / genetics

Substances

  • Bacterial Proteins
  • Polymyxin B

Grants and funding

This work was supported by Fondos del Sistema FEES/CONARE [02-2020, 0652-19 to C. G-V], Fondos FIDA, Universidad Nacional [SIA 0047-17 to C. G-V], Espacio Universitario de Estudios Avanzados, UCREA [B8762] from the Presidency of University of Costa Rica, and the Vice Presidency for Research, University of Costa Rica [C0456 to E.C-O]. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.